ALBERT

Description: INTRODUCTION Hemoglobinopathies, such as sickle cell disease (SCD) and thalassemia, are chronic blood disorders with a profound impact on a patient's life expectancy and quality. Patients often come from marginalized populations with variable health literacy. Prior studies have demonstrated improved outcomes in chronic illness as a result of empowering patients through various education strategies. This systematic review investigates the current state of patient education for SCD and thalassemia with the goal of elucidating which strategies have been effective in improving patient knowledge and/or ability to cope with illness. METHODS Literature was searched up to August 2018 in Medline, PsycINFO, Scopus, CINAHL, Cochrane Central, Cochrane Database of Systematic Reviews, EMBASE, Emcare, and the International Clinical Trials Registry Platform (ICTRP). Randomized controlled trials (RCTs) examining the effects of patient education on patients aged 18 years and older or transitioning into adulthood were included. Psychological interventions were excluded. Preliminary analysis focused on three outcomes: disease knowledge, self-efficacy, and coping ability. Meta-analysis was performed using RevMan 5.3. A random effects model with the inverse variance method was chosen. Standardized mean difference (SMD) was calculated for continuous outcomes due to the different scales used by each study. Changes from baseline with missing standard deviations were imputed from known standard deviations from other studies (Higgins 2011). Heterogeneity was evaluated using the I2 statistic. Domain-based approach was used to assess risk of bias (Higgins 2011). RESULTS The search yielded 12173 citations, 3575 were duplicates. Two reviewers screened the title and abstracts for full text retrieval. Of the 28 full-text citations reviewed, 8 met the inclusion criteria, representing 6 unique RCTs. Of the 6 RCTs, 2 were at high risk of attrition bias. The other domains generally exhibited an unclear risk of bias. Improvement in patient knowledge was a measured outcome in 3 RCTs totalling 351 participants with SCD, mostly of African-American descent. Standard deviations (SD) were lacking in the baseline and 6 month knowledge questionnaire results from Krishnamurti 2018. Attempts to impute the SDs were unsuccessful. Meta-analysis was conducted in the remaining 2 RCTs (n=274). Statistically significant SMD of 0.39 (95% CI 0.05 to 0.72, p=0.02, Figure 1A) in favour of the intervention group with low heterogeneity (I2=24%). These interventions were delivered as either a web-based multimedia education program or in a classroom setting. An increase in self-efficacy was reported in 2 RCTs (n=67) with a statistically significant SMD of 0.72 (95% CI 0.22 to 1.22, p=0.005, Figure 1B) in favour of patient education with no observed statistical heterogeneity (I2=0). Coping ability was reported in 2 RCTs (n=107) but one study was excluded from analysis due to lack of sufficient randomization data. For the remaining study (n=40), the SMD at 0.16 was not statistically significant (95% CI -0.46 to 0.78, p=0.60, Figure 1C). CONCLUSIONS This review summarizes the current state of patient education for adult hemoglobinopathy patients in which some efforts have been made for SCD but no comparable interventions exist for thalassemia. Interventions demonstrated a significant effect on improvement in knowledge and self-efficacy. However, this effect is of uncertain clinical significance due to lack of reporting on clinically relevant illness and healthcare utilization-related outcomes. Only one RCT adequately reported on improvement in coping ability with no statistical significance. Given these results, there is currently insufficient evidence to determine what intervention strategies might benefit adult patients with hemoglobinopathies. This review is limited by the paucity of high-quality RCTs addressing the impact of patient education on self-management. Notably, a considerable volume of studies that employ a non-RCT design were identified and also warrant appropriate analysis. Rigorously designed trials are needed to draw clinically-relevant conclusions regarding type and effectiveness of patient education for adult hemoglobinopathy patients. REFERENCE: Higgins JPT, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Disclosures Kuo: Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy.

Description: Introduction Essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) are a group of hematopoietic stem cell-derived clonal disorders collectively known as the classical, Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Although MPN diagnoses are typically made in the sixth or seventh decade of life, approximately 20% of ET patients and 15% of PV patients are under the age of 40 years. Pregnancy with an MPN is associated with maternal thrombosis, hemorrhage and placental dysfunction leading to fetal growth restriction or loss. The aims of this systematic review were to determine the risk of maternal and fetal complications in pregnancy complicated by MPN and to quantify the benefit of commonly used interventions. Methods A systematic search was conducted using MEDLINE (1946 to July 2018), EMBASE (1947 to July 2018), Cochrane Database of Systematic Reviews (2005 to July 2018), CCRCT (inception to June 2018), and Epub Ahead of Print & Other Non-Indexed Citations (inception to July 2018). Bibliographic references were reviewed for additional studies. There were no date or language restrictions and the review was registered with PROSPERO (CRD42018090680). Studies were included if they reported on maternal or fetal outcomes of pregnancy in patients with an MPN. Case reports and series including fewer than 10 patients were excluded. Duplicate reports were excluded, with only the most recent or most informative included. Data were extracted independently by two investigators (D.M. and S.K.). The primary outcome was live birth. Secondary outcomes included fetal complications (e.g. intrauterine growth restriction) and maternal complications (e.g. pre-eclampsia, thrombosis, hemorrhage). Study quality was assessed using the Newcastle-Ottawa Scale. Analyses were performed using Open Meta-Analyst version 10.12 and Review Manager version 5.3. Results The search strategy resulted in 4191 records of which 22 met the inclusion criteria (Figure 1). The studies included a total of 779 women and 1226 pregnancies. Fifteen of the studies included patients with ET, 3 included patients with PV, and 4 included patients with any classical MPN. There were no studies of MF patients that met our inclusion criteria. Most of the studies were retrospective cohort studies (19) and 3 were prospective cohort studies. Among 1226 pregnancies, the live birth rate was 70%. Of 821 pregnancies with ET and 171 with PV, the live birth rate was 71% and 51%, respectively. The live birth rate was higher in patients with ET who received low dose aspirin during pregnancy than those managed with observation alone (OR 5.0; 95% CI 2.2 - 11.3; I226%; Figure 2). There was no further improvement with the addition of low molecular weight heparin (LMWH) to aspirin (OR 2.8; 95% CI 0.67 - 11.7; I20%). Interferon alpha (INF) during pregnancy was also associated with a higher live birth rate (OR 3.9; 95% CI 1.5 - 10.4; I22.5%; Figure 3). The presence of the JAK2 mutation resulted in a lower live birth rate (OR 0.58; 95% CI 0.4 - 0.9; I26%; Figure 4). Maternal events were unaffected by the addition of aspirin (OR 0.48; 95% CI 0.16 - 1.4; I20%) or INF (OR 0.1; 95% CI 0.01 - 1.5; I20%). Risk of bias assessment was performed using the Newcastle-Ottawa scale. Most studies included a representative cohort and follow up was generally adequate to at least 6 weeks postpartum. Only 3 studies included a control group. Conclusions The preliminary results of our systematic review determined that the live birth rate is lower in pregnant patients with MPN as compared to the general population. The chance of a successful pregnancy was higher in patients with ET than PV and the presence of the JAK2 mutation increased the risk of fetal loss. Patients who received low-dose aspirin during pregnancy had a 5-fold higher odds of a successful pregnancy than those managed with usual care and observation alone. Cytoreduction with INF improved the odds of live birth by nearly 4-fold. Maternal events were uncommon overall and no intervention was found to be beneficial. Our review is limited by generally small sample sizes and the retrospective nature of most studies. Additionally, given that the studies span up to 4 decades, our results may be affected by changing standards of care. Pregnancy in patients with MPN is uncommon and this is the only systematic review to determine the chance of successful pregnancy and quantify the benefit of commonly used interventions. Disclosures Maze: Novartis: Consultancy, Honoraria. Kazi:Shire: Other: Vonvendi was provided by Shire. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding.