Prospective Inception Cohort Study Research Articles

The Institution-Based Prospective Inception Cohort Study: Design, Implementation, and Quality Assurance in Pediatric Thrombosis and Stroke Research

The development of well-designed cohort studies in rare diseases can lead to the discovery of new risk factors and prognostic markers, enhance understanding of natural history and outcomes, and provide preliminary data for randomized controlled trials of treatment strategies. Designing a robust cohort requires substantial upfront design and planning. Ideally, a cohort study of diseased individuals follows patients prospectively from the time of diagnosis (i.e., from the disease's inception). The objective of this article is to discuss the design and implementation of an institution-based prospective inception cohort study, with applied examples in pediatric stroke and thrombosis. Furthermore, we will discuss the ongoing management and quality assurance mechanisms necessary to optimize such a study. Although the resources necessary to implement a prospective inception cohort study are large, this approach can provide critical observational evidence on natural history and prognostic factors. Following multicenter validation, its findings can inform the design and execution of much-needed randomized controlled clinical trials.

Exploring the Distribution and Determinants of a Change in Recovery Expectations Following Traumatic Injury to Victorian Workers

To examine the frequency, distribution and determinants of a change in recovery expectations following non-life threatening acute orthopaedic trauma to Victorian workers. It is proposed that interventions to modify recovery expectations may reduce the burden associated with injury. However, it is not known whether recovery expectations change over time or the factors that are associated with change. A prospective inception cohort study was carried out in which participants were recruited following presentation to hospital for treatment of their injury and followed for 6 months post-injury. Baseline data was obtained by survey and medical record review. Binary logistic regression was used to examine factors associated with a change in recovery expectations between week 2 and week 12 post-injury. The cohort comprised injured workers (n = 145) who had sustained nonlife threatening acute orthopaedic trauma. Factors associated with an improvement in recovery expectations or recovery timeframe included more years of education and higher social functioning. Participants whose injury involved a perception of responsibility by a third party were 7.18 (95 % CI 1.86-27.68) times more likely to change their recovery expectations to more negative expectations and less likely to change to an earlier recovery timeframe. Participants with more severe injuries were more likely to change their recovery timeframe to a longer timeframe. Change in recovery expectations provide some information on injured workers who may benefit from targeted interventions to improve or maintain recovery expectations. The post-injury time-point at which recovery expectations are measured is important if recovery expectations are to inform long-term outcomes.

Peri-procedural bridging with low molecular weight heparin in patients receiving warfarin for venous thromboembolism: A pediatric experience

IntroductionThe incidence of venous thromboembolism (VTE) in children appears to be increasing, and warfarin remains one of the few standard anticoagulants used for secondary VTE prevention. When invasive procedures are required in adults with high TE risk who are receiving warfarin, low-molecular weight heparin (LMWH) bridging is recommended, based mainly upon observational evidence; in children, no such studies have been published. We sought to determine the risks of recurrent TE (both VTE and arterial TE [ATE]) and major bleeding with peri-procedural LMWH bridging in children receiving warfarin for VTE. MethodsChildren (age≤21years of age at the time of bridge) receiving warfarin for VTE and undergoing a standardized clinical care protocol for peri-procedural LMWH bridging were enrolled and followed in an institution-based prospective inception cohort study at Children's Hospital Colorado between March 2006 and February 2012. Outcomes were assessed at 30days post-procedure, and followed International Society on Thrombosis and Haemostasis guidelines. ResultsSeventeen children comprised the cohort, with a total of 23 bridging episodes. Median age at bridging episode was 17.5years (range, 12 to 21years). In 22% of bridging episodes, indication was for major surgery. Median duration of LMWH administration prior to procedure was 6days (range, 4–10days); median duration off anticoagulation peri-procedurally was 1.5days (range: 1–2days). The risks of major bleeding, recurrent VTE, and ATE at 30days post-procedure were 4.3% (1/23), 0% and 0%, respectively. ConclusionsThis study provides important preliminary data on safety and efficacy of perioperative LMWH bridging for adolescent VTE patients receiving warfarin. Larger collaborative pediatric studies are warranted to substantiate these findings and to investigate prognostic factors of bleeding and recurrent TE in this setting.

The epidemiology of polymyalgia rheumatica in primary care: a research protocol.

BackgroundPolymyalgia Rheumatica (PMR) is the commonest inflammatory condition seen in older patients in primary care. To date, however, research has been focused on secondary care cohorts rather than primary care where many patients are exclusively managed. This two year prospective inception cohort study of PMR patients will enable us to understand the full spectrum of this condition.MethodsPatients diagnosed with PMR in primary care will be identified via Read codes and mailed a series of postal questionnaires over a two-year period to assess their levels of pain, stiffness and functioning, as well as medication usage and other health-related and socio-demographic characteristics. In addition, participants will be asked for permission to link their survey data to their general practice electronic medical record and to national mortality and cancer registers.DiscussionThis will be the first large-scale, prospective, observational cohort of PMR patients in primary care. The combination of survey data with medical records and national registers will allow for a full investigation of the natural history and prognosis of this condition in the primary care setting, in which the majority of patients are treated, but where little research on the treatment and outcome of consultation has been undertaken. This will provide information that may lead to improved primary care management of PMR.

Low Back Pain in Time: Risk Factors Associated with Persistence, Recurrence, and Time Till Patients Seek Help in Primary Care

Introduction Time characteristics of early episodes of low back pain (LBP) like duration and recurrence may relate to current risk factors and lack of resources that increase the risk of persistent LBP. In addition, when suffering from a first episode of LBP and individuals decide to seek medical care, time till individuals do should be not too long. Again, delay of presentation may relate to risk factors and lack of resources. Aim of our study was to estimate the relationship between time-related LBP characteristics and prognostic factors for acute/subacute LBP in primary care. Materials and Methods Prospective inception cohort study of 315 consecutive patients attending a health practitioner for their first episode of acute/subacute LBP or recurrent LBP. One-tailed correlations conducted between patient characteristics and the three time-related characteristics “subacute LBP”, “recurrent LBP,” and “delayed presentation”. Results The pattern of correlation between risk factors and resources against persistent LBP differed between three time-related variables. “Subacute LBP” and “delayed presentation” were positively associated with psychological factors (pain catastrophizing, magnification, and helplessness). Both indicators were negatively correlated with resources (job satisfaction and time control) against development of persistent LBP. Moreover, “delayed presentation” was related positively with occupational stressors (“resigned attitude towards the job”, “uncertainty”, “problem with organization of work tasks”, “work interruptions”). In contrast, “recurrent LBP” was only related to more impaired health-related factors (functional limitation, sensory, and affective pain). Conclusion Patients with current LBP waiting longer till seeking help in primary care have a more disadvantageous profile of occupational and psychological risk factors and lower resource levels. A similar but less pronounced pattern occurred in those with subacute LBP compared to those with acute LBP. Implications for clinical practice are twofold; (1) LBP-patients with prolonged symptoms or delayed care-seeking behavior, who are at risk of developing persistent LBP, should be screened for psychological factors such as magnification and helplessness, (2) In these patients, occupational resources like job satisfactionand time control should be addressed and strengthened in primary and secondary prevention, where feasible. Future research should examine time-related variables that influence prognostic factors for LBP in different clinical settings such as predominantly retired or unemployed populations. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared

Treatment, Survival, and Thromboembolic Outcomes of Thrombotic Storm in Children

To describe the course and management of thrombotic storm in 8 children. Clinical data were collected and analyzed for consecutive children diagnosed with thrombotic storm, aged 6 months to 21 years inclusive, in the context of a single-institution prospective inception cohort study. Thrombotic storm was defined as newly diagnosed multisite venous thromboembolism (VTE) with acute thrombus progression despite conventional or higher than conventional dosing of heparin or low molecular weight heparin. All evaluations and therapies were ordered by the treating physicians in the context of clinical decision making. Eight of the 178 children with VTE enrolled in the cohort between March 2006 and November 2009 were diagnosed with thrombotic storm. Antiphospholipid antibodies were acutely positive in 6 children, of whom heparin-induced thrombocytopenia was confirmed by serotonin release assay in 2 and atypical in 1. One child died. Five children received a direct thrombin inhibitor, titrated to achieve normalization of markedly elevated D-dimer levels. All children were transitioned to fondaparinux or enoxaparin before receiving extended anticoagulation with warfarin. Immunomodulatory therapy was instituted in all children. During follow-up (median duration, 3 years; range, 2-6 years), 3 of the 7 surviving children experienced recurrent VTE, and 4 children had clinically significant postthrombotic syndrome. Thrombotic storm is an infrequent but potentially fatal presentation of VTE in children. Administration of direct thrombin inhibitors and immune modulation can achieve quiescence, although long-term adverse outcomes are common.

Monitoring hypercoagulability and hypofibrinolysis following acute venous Thromboembolism in Children: Application of the CloFAL assay in a prospective inception cohort study

Although individual thrombophilia tests are frequently performed in children with venous thromboembolism (VTE), global assays provide the opportunity to fill the gap in knowledge regarding their net impact on overall coagulative (and in some cases fibrinolytic) function. We first evaluated analytic sensitivity of the Clot Formation and Lysis (CloFAL) global assay to hypercoagulability and alterations in fibrinolysis, and then characterized changes in plasma coagulative and fibrinolytic capacities over time in children with acute VTE. In plasma ex vivo and in vitro experiments, the CloFAL assay area-under-the-curve (AUC) was analytically sensitive to hypercoagulable states, and its modified fibrinolytic index (FI2) was sensitive to both hyper- and hypofibrinolytic conditions. Clinical data and plasma samples for assay were collected during follow-up of 50 children enrolled in a prospective inception cohort study of VTE from May 2006 to June 2010. Follow-up periods were designated as follows: acute (<1month post-event), sub-acute (1–3months), early chronic (3–12months), and late chronic (>12months). Since most children were sampled at fewer than three pre-defined follow-up periods, study population findings were grouped by timepoint. AUC was significantly increased, and FI2 significantly decreased, in the acute period of VTE when compared to healthy controls, indicating hypercoagulability and hypofibrinolysis, respectively. One-third of patients were hypercoagulable, and 23% were hypofibrinolytic, in the late chronic phase. AUC and FI2 were strongly correlated with functional fibrinogen levels. These findings indicate the utility of the CloFAL assay in monitoring plasma coagulative and fibrinolytic capacities in children with VTE. Studies of its potential role in outcome prediction are ongoing.

Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study

ObjectiveThe aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).MethodsThe Systemic Lupus International Collaborating Clinics, or SLICC, performed a...

Why patients consume opioids post surgery

Determinants of the duration of opioid use after surgery are under- reported. We hypothesized that independent of pain, validated measures of preoperative psychological distress would predict more durable and prolonged opioid use following surgery. Between January 2007 and April 2009 a prospective longitudinal inception cohort study measured psychological distress and substance abuse preoperatively, and opioid use longitudinally following surgery. 109 of 134 consecutively approached patients scheduled to undergo mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement consented to participate.

Cerebral Microbleeds on Magnetic Resonance Imaging and Anticoagulant-Associated Intracerebral Hemorrhage Risk

The increasing use of antithrombotic drugs in an aging population [including anticoagulants to prevent future ischemic stroke in individuals with atrial fibrillation (AF)] has been associated with a dramatic increase in the incidence of intracerebral hemorrhage (ICH) in users of antithrombotic drugs. Several lines of evidence suggest that cerebral small vessel disease (particularly sporadic cerebral amyloid angiopathy) is a risk factor for this rare but devastating complication of these commonly used treatments. Cerebral microbleeds (CMBs) have emerged as a key MRI marker of small vessel disease and a potentially powerful marker of future ICH risk, but adequately powered, high quality prospective studies of CMBs and ICH risk on anticoagulation are not available. Further data are urgently needed to determine how neuroimaging and other biomarkers may contribute to individualized risk prediction to make anticoagulation as safe and effective as possible. In this review we discuss the available evidence on cerebral small vessel disease and CMBs in the context of antithrombotic treatments, especially regarding their role as a predictor of future ICH risk after ischemic stroke, where risk-benefit judgments can be a major challenge for physicians. We will focus on patients with AF because these are frequently treated with anticoagulation. We briefly describe the rationale and design of a new prospective observational inception cohort study (Clinical Relevance of Microbleeds in Stroke; CROMIS-2) which investigates the value of MRI markers of small vessel disease (including CMBs) and genetic factors in assessing the risk of oral anticoagulation-associated ICH.

Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic.

IntroductionThe specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs.MethodsWe conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden.ResultsAmong the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas.ConclusionsThe peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.

Nutrition and dietary behaviors in pediatric Inflammatory Bowel Disease

Nutrition and health behaviors are important to the development and health outcomes of children with chronic illnesses. Given the concerns related to growth and bone health, nutrition and healthy dietary behaviors are especially important in Pediatric Inflammatory Bowel Disease (Pedi IBD). Concerns related to nutrition in Pedi IBD have led investigators to make specific recommendations related to increased nutrient intakes. Although research examining nutrition supplementation or enteral rescue therapy in Pedi IBD has demonstrated a positive impact on IBD health outcomes, the Pedi IBD literature is lacking in research evaluating daily oral nutrition and health behaviors. It is important to examine nutrition and health behaviors in Pedi IBD in order to maximize health-promotion and IBD health outcomes. To examine daily oral nutrition, including caloric and nutrient intake and dietary behaviors, in Pedi IBD. Preliminary baseline food frequency data was derived from OSCCAR, the prospective inception cohort study examining only residents of Rhode Island. Children from 9:0 to 17:11 years old (N=58) were included in the analyses. Daily nutrient intake estimates included reported use of supplements. One sample t-tests were used to compare nutrient intake to daily intake recommendations from the Crohn's and Colitis Foundation of America (CCFA). Frequencies of fruit, vegetable, milk, and snack foods were examined and described in terms of weekly consumption. Average caloric intake was estimated to be 2310 kcal per day. Estimated daily vitamin D intake (M=355 iu) was significantly below the expected CCFA norm of 800 iu, t(57) = -13.95, p = .000. Estimated daily calcium intake (M=1263 mg) was significantly below the expected CCFA norm of1500 mg, t(57) = -2.97, p = .004. Fifty-five percent and 30% reported less than weekly consumption of more than 1 type of fruit and 1 type of vegetable, respectively. Of the 3 most frequently consumed fruits (apples, bananas, and grapes), 55%, 57%, and 79% reported consuming less than one portion per week, respectively. Of the 3 most frequently consumed vegetables (tomato sauce, corn, iceberg lettuce), 50%, 53%, 62% reported consuming less than one portion per week, respectively. Fifty percent of the participants reported consuming less than 2 glasses of milk per day. Seventy-five percent reported consuming cookies and 40% reported consuming potato chips at least weekly. Nutrient intake in Pedi IBD appears to fall below recommended intakes due to lack of healthy dietary behaviors. Given the potential impact nutrition may have on IBD health outcomes, including growth and development, it is important for future research to 1) examine factors that promote healthy dietary behaviors and adherence to dietary recommendations in Pedi IBD; 2) examine the relationship between nutrition, dietary behaviors, and IBD health outcomes, including long-term dietary trends and outcomes; and 3) develop behavioral interventions to maximize nutrition in Pedi IBD.

Bypassing Agents in Children with Inhibitors: How Much Do We Use and How Much Is Too Much?

Abstract 1217 Background:Children with hemophilia A and high-titer inhibitors suffer frequent severe bleeding events and often respond to bypassing agents more poorly than adults resulting in increased dosing and cost. Aims: This study was conducted to determine the amount and variability of bypass agent therapy currently given to children with inhibitors at a large combined adult and pediatric hemophilia treatment center in comparison to treatment of adult inhibitor patients. Methods: All subjects were enrolled onto a single institution prospective inceptional cohort study of bleeding disorders with appropriate IRB-approved consent and assent. All children who developed high-titer inhibitors were treated with immune tolerance induction, and children treated with bypassing agents primarily represent difficult inhibitors. Data regarding treatment agents, dose and duration were extracted for 24 bleeding events in 6 children in comparison to comparable data on 26 bleeding events in 5 adults with high-titer inhibitors. Treatment decisions were made clinically by academic hematologists in consultation with hemophilia nurses, patients and parents based on perceived severity of bleeding events and therapeutic response. Treatment was given as recombinant factor VIIa (NovoSeven, N, n=28), prothrombin complex concentrates (FEIBA, F, n=10) or alternating doses of both (A, n=12). Median results for individual children and aggregated adult data are shown on Table 1. Children received seven times the treatment doses and duration compared with adults. In addition, children received both N and F for half of the bleeding events, while this was used for only one adult event. Treatment duration in children was not affected by initial dose or dose frequency of N (p > 0.05 for both). Bleeding events were severe and difficult to manage; significant long-term morbidity in these 6 children include ankle arthropathy in 3, elbow contracture following compartment syndrome in 2 and quadrucep pseudotumor in 1. [Display omitted] Discussion:Children with hemophilia A and inhibitors experience bleeding episodes that are poorly responsive to both N and F, resulting in higher dosing, longer duration and enormous costs. Children require better inhibitor therapies. Clinical trials of new bypassing agents designed specifically for children are urgently needed. Disclosures:No relevant conflicts of interest to declare.

Concentrate-related inhibitor risk: is a difference always real?

See also Aledort LM, Navickis RJ, Wilkes MM. Can B-domain deletion alter the immunogenicity of recombinant factor VIII? A meta-analysis of prospective clinical studies. This issue, pp 2180–92.

Predictors of disability in children with inflammatory arthritis, two and three years after first presentation to paediatric rheumatology. Results from the childhood arthritis prospective study (CAPS)

Background Inflammatory arthritis (IA) in children is a chronic and often disabling disease with variable outcome. Up to 1/3 of children are reported to have active disease progressing into adulthood. The Childhood Arthritis Prospective Study (CAPS) is a prospective longitudinal inception cohort study which aim is to identify genetic and environmental predictors of shortand long-term outcome of childhood IA. Previously, we reported that the strongest predictor of persistent disability at oneyear (as measured by the CHAQ) was moderate to severe disability at first presentation. The objective of this study was to extend the one year analysis to look at both two and three year outcomes.

Decreased live births in women with systemic lupus erythematosus

Multiple disease-related factors may limit the number of children born to women with systemic lupus erythematosus (SLE). We calculated live births in women with SLE and compared this with general population rates. We studied women with SLE from a subset of centers participating in the Systemic Lupus International Collaborating Clinics Prospective Inception Cohort Study of SLE. Women diagnosed as having SLE before age 50 years were included. Using age, calendar-period, and country-specific general population birth rates, we calculated the standardized incidence ratio (SIR) of observed to expected live births. We also performed a multivariate analysis with the SIR as the dependent variable to explore potential predictors of live births. A total of 339 women with SLE were studied. The number of live births over the interval (n = 313) was substantially below that which would be expected (n = 479; SIR 0.65, 95% confidence interval [95% CI] 0.58-0.73). In the multivariate analyses, black race/ethnicity (SIR 1.47, 95% CI 1.08-2.00) and being married or living common-law (SIR 2.04, 95% CI 1.52-2.74) were associated with increased live births (relative to what would be expected). There were trends for fewer live births in women exposed to cyclophosphamide (SIR 0.88, 95% CI 0.56-1.38) and in those with high disease activity (mean SLE Disease Activity Index 2000 update score ≥5; SIR 0.82, 95% CI 0.54-1.25). Overall, we found that women with SLE have fewer live births compared with the general population. Marital status, race/ethnicity, and possibly clinical factors may mediate this effect.

Persistent Shoulder Pain in the First 6 Months After Stroke: Results of a Prospective Cohort Study

Roosink M, Renzenbrink GJ, Buitenweg JR, Van Dongen RT, Geurts AC, IJzerman MJ. Persistent shoulder pain in the first 6 months after stroke: results of a prospective cohort study. Objective To identify factors associated with persistent poststroke shoulder pain (pPSSP) in the first 6 months after stroke. Design Prospective inception cohort study. Setting Stroke units of 2 teaching hospitals. Participants Patients (N=31) with a clinical diagnosis of stroke. Interventions Not applicable. Main Outcome Measures The development of pPSSP within the first 6 months after stroke. Clinical assessment of motor, somatosensory, cognitive, emotional, and autonomic functions, undertaken within 2 weeks (t0), at 3 months (t1), and at 6 months (t2) after stroke. Results Patients with pPSSP (n=9) were compared with patients without pPSSP (n=22). Bivariate logistic regression analyses showed that pPSSP was significantly associated with impaired voluntary motor control (t0, t1, t2), diminished proprioception (t0, t1), tactile extinction (t0), abnormal sensation (t1, t2), spasticity of the elbow flexor muscles (t1, t2), restricted range of motion (ROM) for both shoulder abduction (t2) and shoulder external rotation (t1, t2), trophic changes (t1), and type 2 diabetes mellitus (t0). Conclusions These findings suggest a multifactorial etiology of pPSSP. The association of pPSSP with restricted, passive, pain-free ROM and signs indicative of somatosensory sensitization may implicate a vicious cycle of repetitive (micro)trauma that can establish itself rapidly after stroke. Intervention should therefore be focused on maintaining and restoring joint ROM as well as preventing injury and somatosensory sensitization. In this perspective, strategies that aim to intervene simultaneously at various levels of function can be expected to be more effective than treatment directed at merely 1 level.

Incidence of Tardive Dyskinesia with Risperidone or Olanzapine in the Elderly: Results from a 2-Year, Prospective Study in Antipsychotic-Naïve Patients

Tardive dyskinesia (TD) rates with second-generation antipsychotics (SGAs) are considered to be low relative to first-generation antipsychotics (FGAs), even in the particularly vulnerable elderly population. However, risk estimates are unavailable for patients naïve to FGAs. Therefore, we aimed to determine the TD incidence in particularly vulnerable, antipsychotic-naïve elderly patients treated with the SGA risperidone or olanzapine. The present work describes a prospective inception cohort study of antipsychotic-naïve elderly patients aged 55 years identified at New York Metropolitan area in-patient and out-patient geriatric psychiatry facilities and nursing homes at the time of risperidone or olanzapine initiation. At baseline, 4 weeks, and at quarterly periods, patients underwent assessments of medical and medication history, abnormal involuntary movements, and extra-pyramidal signs. TD was classified using Schooler-Kane criteria. Included in the analyses were 207 subjects (age: 79.8 years, 70.0% female, 86.5% White), predominantly diagnosed with dementia (58.9%) or a major mood disorder (30.9%), although the principal treatment target was psychosis (78.7%), with (59.4%) or without (19.3%) agitation. With risperidone (n=159) the cumulative TD rate was 5.3% (95% confidence interval (CI): 0.7, 9.9%) after 1 year (mean dose: 1.0±0.76 mg/day) and 7.2% (CI: 1.4, 12.9%) after 2 years. With olanzapine (n=48) the cumulative TD rate was 6.7% (CI: 0, 15.6%) after 1 year (mean dose: 4.3±1.9 mg/day) and 11.1% (CI: 0, 23.1%) after 2 years. TD risk was higher in females, African Americans, and patients without past antidepressant treatment or with FGA co-treatment. The TD rates for geriatric patients treated with risperidone and olanzapine were comparable and substantially lower than previously reported for similar patients in direct observation studies using FGAs. This information is relevant for all patients receiving antipsychotics, not just the especially sensitive elderly.

Percutaneous Mechanical and Pharmacomechanical Thrombolysis for Occlusive Deep Vein Thrombosis of the Proximal Limb in Adolescent Subjects: Findings from an Institution-based Prospective Inception Cohort Study of Pediatric Venous Thromboembolism

Purpose Young individuals with occlusive, proximal-limb deep vein thrombosis (DVT) who have acutely increased plasma levels of factor VIII and D-dimer are at high risk for postthrombotic syndrome (PTS) when treated with conventional anticoagulation alone. The present report is an evaluation of experience with adjunctive percutaneous mechanical thrombolysis (PMT) and/or percutaneous pharmacomechanical thrombolysis (PPMT) in such patients. Patients and Methods Among 95 children 11–21 years of age enrolled in a prospective cohort of venous thromboembolism between March 1, 2006, and November 1, 2009, 16 met eligibility criteria and underwent PMT/PPMT, typically with adjunctive catheter-directed thrombolytic infusion (CDTI) of tissue-type plasminogen activator given after the procedure. Results Median age was 16 years (range, 11–19 y). Thirteen cases (81%) involved lower limbs. Underlying stenotic lesions were disclosed in 53%, with endovascular stents deployed in all cases of May–Thurner anomaly. There were no periprocedural major bleeding events and one symptomatic pulmonary embolism. Technical success rate was 94%. Early (< 30 days) locally recurrent DVT developed in 40% of cases, of which 83% were successfully treated with repeat lysis. Late recurrent DVT rate (median follow-up duration, 14 months; range, 1–42 mo) was 27%. Cumulative incidence of physically and functionally significant PTS at 1–2 years was 13%. Conclusions This experience provides preliminary evidence that PMT/PPMT with adjunctive CDTI can be used safely and effectively in adolescent subjects with DVT at high risk for PTS.

Percutaneous Mechanical and Pharmacomechanical Thrombolysis for Occlusive Deep Vein Thrombosis of the Proximal Limb in Adolescent Subjects: Findings from an Institution-based Prospective Inception Cohort Study of Pediatric Venous Thromboembolism

Percutaneous Mechanical and Pharmacomechanical Thrombolysis for Occlusive Deep Vein Thrombosis of the Proximal Limb in Adolescent Subjects: Findings from an Institution-based Prospective Inception Cohort Study of Pediatric Venous Thromboembolism