Congenital dyserythropoietic anemia type IV in the genetic era: A rare neonatal case report of rapid identification with a review of the literature.

Congenital dyserythropoietic anemia type IV (CDAIV) is a rare inherited hematological disorder, presenting with severe anemia due to altered erythropoiesis and hemolysis, with variable needs for recurrent transfusions. We present a case of a transfusion-dependent male newborn who presented at birth with severe hemolytic anemia, and required an intrauterine transfusion. Genetic testing rapidly identified a Kruppel-like factor 1 (KLF1) pathogenic variant (c.973G>A, p.E325K), known to be causative for CDAIV. This case highlights the advantages of next-generation sequencing testing for congenital hemolytic anemia: diagnostic speed, guidance on natural history, and optimized clinical management and anticipatory guidance for parents and clinicians. Additionally, we reviewed the literature for all CDAIV cases.

Reassessing the Need for Preoperative Transfusions in Sickle Cell Disease Patients With an Elevated Baseline Hemoglobin-A Retrospective Study.

BACKGROUND: Current guidelines recommend a preoperative hemoglobin of 10.0 g/dL in patients with sickle cell disease [SCD], however, this threshold continues to be an area of controversy. Previous studies demonstrating the benefits of preoperative transfusions have largely not captured patients with elevated baseline hemoglobin, in part due to low hydroxyurea uptake and exclusion of nonhemoglobin SS SCD. MATERIALS AND METHODS: We conducted a retrospective chart review of patients with SCD <18 years of age undergoing low and medium-risk procedures at 2 academic medical centers in Canada between 2007 and 2017. The primary objective was to study the association of preoperative transfusion on postoperative complications in patients with SCD with baseline hemoglobin between 9.0 and 10.0 g/dL. Multivariable logistic regression was used to estimate the adjusted effect of preoperative transfusion on the risk of developing postoperative complications. RESULTS: In all, 159 procedures in patients with hemoglobin <9.0 g/dL [Hb <9.0 ] and 173 procedures in patients with hemoglobin between 9.0 and 10.0 g/dL [Hb 9.0-10.0 ] were analyzed. In the absence of preoperative transfusion, Hb 9.0-10.0 patients had lower overall complications [23% vs. 34%] compared with Hb <9.0 patients [OR 0.29, 95% CI 0.12-0.72, P =0.008]. In total, 75% of Hb <9.0 and 21% of Hb 9.0-10.0 patients received a preoperative simple transfusion. Transfusion was associated with increased risk of postoperative complications in Hb 9.0-10.0 [OR 3.02, 95% CI 1.26-7.23, P =0.013], but not Hb <9.0 patients [OR 0.64, 95% CI 0.28-1.45, P =0.30]. CONCLUSIONS: Simple transfusion may not be warranted in Hb 9.0-10.0 patients undergoing low-risk procedures. Prospective studies validating these findings are needed.

Health services use by children identified as heterozygous hemoglobinopathy mutation carriers via newborn screening.

BACKGROUND: Newborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results. METHODS: Eligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls. RESULTS: Adjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children < 1 year of age were: 1.11 (1.06-1.17) for ED visits; 0.97 (0.89-1.06) for inpatient hospitalization; and 1.02 (1.00-1.04) for physician encounters. Among children ≥1 year of age, adjusted rate ratios were: 1.03 (0.98-1.07) for ED visits; 1.14 (1.03-1.25) for inpatient hospitalization and 0.92 (0.90-0.94) for physician encounters. CONCLUSIONS: While we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood.

Pediatric Oncology Clinic Care Model: Achieving Better Continuity of Care for Patients in a Medium-sized Program.

Providing the best care in both the inpatient and outpatient settings to pediatric oncology patients is all programs goal. Using continuous improvement methodologies, we changed from a solely team-based physician care model to a hybrid model. All patients were assigned a dedicated oncologist. There would then be 2 types of weeks of outpatient clinical service. A "Doc of the Day" week where each oncologist would have a specific day in clinic when their assigned patients would be scheduled, and then a "Doc of the Week" week where one physician would cover clinic for the week. Patient satisfaction surveys done before and 14 months after changing the model of care showed that patients were very satisfied with the care they received in both models. A questionnaire to staff 14 months after changing showed that the biggest effect was increased continuity of care, followed by more efficient clinic workflow and increased consistency of care. Staff felt it provided better planning and delivery of care. A hybrid model of care with a primary physician for each patient and assigned clinic days, alternating with weeks of single physician coverage is a feasible model of care for a medium-sized pediatric oncology program.

Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia.

BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory allo-antibodies and for prophylaxis and treatment of patients with congenital factor VII deficiency. It is also used for off-license indications to prevent bleeding in operations where blood loss is likely to be high, and/or to stop bleeding that is proving difficult to control by other means. This is the third version of the 2007 Cochrane review on the use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia, and has been updated to incorporate recent trial data. OBJECTIVES: To assess the effectiveness of rFVIIa when used therapeutically to control active bleeding or prophylactically to prevent (excessive) bleeding in patients without haemophilia. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other medical databases up to 23 March 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any patient population (except haemophilia). Outcomes were mortality, blood loss or control of bleeding, red cell transfusion requirements, number of patients transfused and thromboembolic adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently assessed potentially relevant studies for inclusion, extracted data and examined risk of bias. We considered prophylactic and therapeutic rFVIIa studies separately. MAIN RESULTS: Twenty-nine RCTs were included: 28 were placebo-controlled, double-blind RCTs and one compared different doses of rFVIIa. In the 'Risk of bias' assessment, most studies were found to have some threats to validity although therapeutic RCTs were found to be less prone to bias than prophylactic RCTs.Sixteen trials involving 1361 participants examined the prophylactic use of rFVIIa; 729 received rFVIIa. There was no evidence of mortality benefit (risk ratio (RR) 1.04; 95% confidence interval (CI) 0.55 to 1.97). There was decreased blood loss (mean difference (MD) -297 mL; 95% CI -416 to -178) and decreased red cell transfusion requirements (MD -261 mL; 95% CI -367 to -154) with rFVIIa treatment; however, these values were likely overestimated due to the inability to incorporate data from trials (four RCTs in the outcome of blood loss and three RCTs in the outcome of transfusion requirements) showing no difference of rFVIIa treatment compared to placebo. There was a trend in favour of rFVIIa in the number of participants transfused (RR 0.85; 95% CI 0.72 to 1.01). However, there was a trend against rFVIIa with respect to thromboembolic adverse events (RR 1.35; 95% CI 0.82 to 2.25).Thirteen trials involving 2929 participants examined the therapeutic use of rFVIIa; 1878 received rFVIIa. There were no outcomes where any observed advantage or disadvantage of rFVIIa over placebo could not have been observed by chance alone. There was a trend in favour of rFVIIa for reducing mortality (RR 0.91; 95% CI 0.78 to 1.06). However, there was a trend against rFVIIa for increased thromboembolic adverse events (RR 1.14; 95% CI 0.89 to 1.47).When all trials were pooled together to examine the risk of thromboembolic events, a significant increase in total arterial events was observed (RR 1.45; 95% CI 1.02 to 2.05). AUTHORS' CONCLUSIONS: The effectiveness of rFVIIa as a more general haemostatic drug, either prophylactically or therapeutically, remains unproven. The results indicate increased risk of arterial events in patients receiving rFVIIa. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.

Exploring the Needs of Adolescents With Sickle Cell Disease to Inform a Digital Self-Management and Transitional Care Program: Qualitative Study.

BACKGROUND: Accessible self-management interventions are critical for adolescents with sickle cell disease to better cope with their disease, improve health outcomes and health-related quality of life, and promote successful transition to adult health care services. However, very few comprehensive self-management and transitional care programs have been developed and tested in this population. Internet and mobile phone technologies can improve accessibility and acceptability of interventions to promote disease self-management in adolescents with sickle cell disease. OBJECTIVE: The aim of this study was to qualitatively explore the following from the perspectives of adolescents, parents, and their health care providers: (1) the impact of sickle cell disease on adolescents to identify challenges to their self-management and transitional care and (2) determine the essential components of a digital self-management and transitional care program as the first phase to inform its development. METHODS: A qualitative descriptive design utilizing audio-recorded, semistructured interviews was used. Adolescents (n=19, aged 12-19 years) and parents (n=2) participated in individual interviews, and health care providers (n=17) participated in focus group discussions and were recruited from an urban tertiary care pediatric hospital. Audio-recorded data were transcribed verbatim and organized into categories inductively, reflecting emerging themes using simple content analysis. RESULTS: Data were categorized into 4 major themes: (1) impact of sickle cell disease, (2) experiences and challenges of self-management, (3) recommendations for self-management and transitional care, and (4) perceptions about a digital self-management program. Themes included subcategories and the perspectives of adolescents, parents, and health care providers. Adolescents discussed more issues related to self-management, whereas health care providers and parents discussed issues related to transition to adult health services. CONCLUSIONS: Adolescents, parents, and health care providers described the continued challenges youth with sickle cell disease face in terms of psychosocial impacts and stigmatization. Participants perceived a benefit to alleviating some of these challenges through a digital self-management tool. They recommended that an effective digital self-management program should provide appropriate sickle cell disease-related education; guidance on developing self-advocacy and communication skills; empower adolescents with information for planning for their future; provide options for social support; and be designed to be engaging for both adolescents and parents to use. A digital platform to deliver these elements is an accessible and acceptable way to address the self-management and transitional care needs of adolescents.

Quality of life after acute myocardial infarction: a comparison of diabetic versus non-diabetic acute myocardial infarction patients in Quebec acute care hospitals.

BACKGROUND: Previous studies have evaluated the individual effects of acute myocardial infarction (AMI) and diabetes mellitus on health-related quality of life outcomes (QOL). Due to the rising incidence of these comorbid conditions, it is important to examine the synergistic impact of diabetes mellitus and AMI on QOL. METHODS: In this study, we assessed using several previously validated questionnaires the QOL and functional status of 96 diabetic patients and 491 non-diabetic patients admitted to Quebec hospital sites with AMI between 1997 and 1998. We also conducted multivariate analyses to ascertain whether diabetes mellitus was an independent determinant of SF-36 physical functioning (PCS) and mental health (MCS) component score QOL outcomes after AMI. RESULTS: Both patient groups had similar baseline clinical characteristics, but diabetic patients had slightly higher rates of cardiac risk factors compared to non-diabetics. Overall, QOL measures were similar between both patient groups at baseline, but diabetic patients reported poorer functional status than non-diabetic patients. Over the study period, there were significant differences between the QOL and functional status of diabetic and non-diabetic populations. By one year, diabetic patients reported poorer QOL outcomes than non-diabetic patients. However, diabetic patients showed greater improvements in their functional status, but were less likely to return to work compared to non-diabetic patients. In contrast with these findings, our multivariate analyses showed that diabetes mellitus was not an independent determinant of QOL and functional status. CONCLUSION: Our study findings suggest that diabetes mellitus is not an independent determinant of QOL after AMI.

Drug prescriptions after acute myocardial infarction: dosage, compliance, and persistence.

BACKGROUND: Although it has been well documented that aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and lipid-lowering drugs are under-prescribed for patients with acute myocardial infarction (Am Heart J 2003;145:438-44.), few studies have examined dosage and long-term compliance and persistence patterns for the use of these drugs after AMI. METHODS: Using Quebec administrative data on all elderly (aged > or =65 years) survivors of hospital admissions for AMI between 1996 and 1998 (n = 14,057), we studied the discharge prescriptions, dosages, patient compliance, and persistence during this period for aspirin, beta-blockers, ACE inhibitors, and lipid-lowering drugs. RESULTS: Rates of discharge medications were suboptimal (aspirin 65%, beta-blockers 54%, ACE inhibitors 45%, lipid-lowering drugs 21%). Most patients with prescriptions for aspirin and ACE inhibitors were prescribed dosages equivalent to those administered in clinical trials (99% and 88%, respectively). In contrast, only 20% of patients with beta-blocker prescriptions and 48% of patients with lipid-lowering drug prescriptions were prescribed clinical trial doses. For patients with discharge prescriptions, 1-year compliance rates were high (aspirin 74%, beta-blockers 74%, ACE inhibitors 70%, lipid-lowering drugs 84%), as were the 1-year persistence rates (aspirin 71%, beta-blockers 72%, ACE inhibitors 69%, lipid-lowering drugs 80%). CONCLUSION: Although cardiac drugs are under-prescribed to patients with AMI, once prescribed, patients are likely to adhere to these prescriptions, with high rates of compliance and persistence.

Quality of life after acute myocardial infarction: a systematic review.

BACKGROUND: Health-related quality of life (HRQoL) is an important measure of a patient's recovery after an illness. It has been suggested that different treatments may affect the HRQoL of patients with acute myocardial infarction (AMI). OBJECTIVE: To examine the effects of an AMI on HRQoL and identify common patterns in the HRQoL assessments of post-AMI patients. METHODS: Systematic review of published studies. RESULTS: The impact of AMI on HRQoL appears to be modest. Physical capacity, work status, symptoms, functional status and general health perceptions declined the most after AMI. However, the majority of these HRQoL domains improved to normal levels with time. The severity of AMI-related symptoms, timing of HRQoL measurements after AMI and patients' age have had the most important influence on patient HRQoL after AMI. CONCLUSIONS: The review suggests that HRQoL is minimally affected by AMI. However, current measurement tools may not be sensitive enough to detect changes in HRQoL after AMI.

Regional variation in the management of acute myocardial infarction in the province of Quebec.

BACKGROUND: Previous studies have shown that there are differences in acute myocardial infarction (AMI) management in Canada and in the United States. However, there has been little research to evaluate regional variations in AMI treatment and outcomes for Canadian patients. OBJECTIVE: To determine whether regional variation in the management of AMI in Quebec has an impact on patient mortality and morbidity. PATIENTS AND METHODS: Discharge summary and physician claims databases for 76,012 patients with AMI were used between January 1, 1988 and December 31, 1995 to build 16 cohorts for the administrative regions of the province of Quebec. The clinical characteristics, prescription medications, cardiac procedure use, readmissions for cardiac complications and mortality across the different regions were compared. RESULTS: After adjusting for age and sex, discharge prescriptions resulted in the following ranges: angiotensin-converting enzyme inhibitors 34% to 46% of patients, acetylsalicylic acid 49% to 77%, beta-blockers 32% to 54%, calcium channel blockers 25% to 48%, lipid-lowering drugs 4% to 16% and nitrates 76% to 86%. Procedure use varied considerably across the province during the initial 10 days post-AMI (catheterization 3% to 28%; percutaneous coronary intervention 1% to 8%, and coronary artery bypass surgery 0 to 2%), as well as one year after discharge (27% to 47%, 8% to 17%, and 6% to 12%, respectively). Some variation was observed for cardiac complications after one year (unstable angina 9% to 21%; congestive heart failure and recurrent myocardial infarction, no major variation). However, there was no significant regional variation observed for one-year and three-year mortality rates (19% to 22% and 27% to 31%, respectively). CONCLUSIONS: There was marked regional variation in the rates of discharge prescriptions for cardiac medications and cardiac procedures in patients who have had an AMI in Quebec. These results suggest that the type of treatment received for an AMI depends on the region in which the patient lives. This variation appeared to affect readmission rates for unstable angina, but had no impact on mortality or other cardiac complications post-AMI.

Neonatal renal vein thrombosis.

Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.