Baseline characteristics and outcomes of children with cancer in the English-speaking Caribbean: A multinational retrospective cohort.

BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. RESULTS: A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5.7 years (interquartile range 2.9-10.6 years). One hundred thirty (35.4%) patients were diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with solid tumors. A relative paucity of children with brain tumors was seen (N = 58, 15.8%). Two-year event-free survival (EFS) for the cohort was 48.5% ± 3.2%; 2-year overall survival (OS) was 55.1% ± 3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumor (WT) experienced better 2-year EFS (62.1% ± 6.4% and 66.7% ± 10.1%), while dismal outcomes were seen in children with acute myeloid leukemia (AML; 22.7 ± 9.6%), rhabdomyosarcoma (21.0% ± 17.0%), and medulloblastoma (21.4% ± 17.8%). Of 108 deaths with known cause, 58 (53.7%) were attributed to disease and 50 (46.3%) to treatment complications. Death within 60 days of diagnosis was relatively common in acute leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators adversely impacted outcome in ALL, including higher age, higher white blood cell count, and T-cell lineage. CONCLUSIONS: ESC childhood cancer outcomes are significantly inferior to high-income country outcomes. Based on these data, interventions for improving supportive care and modifying treatment protocols are under way. Continued data collection will allow evaluation of interventions and ensure maximal outcome improvements.

Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and clinical manifestations.

UNLABELLED: Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. OBJECTIVES: Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. METHODS: A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. RESULTS: CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. CONCLUSIONS: There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE.

HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Influenza vaccination in the organ transplant recipient: review and summary recommendations.

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Guidance on novel influenza A/H1N1 in solid organ transplant recipients.

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.

Exploring beyond viral load testing for EBV lymphoproliferation: role of serum IL-6 and IgE assays as adjunctive tests.

We examined serum IL-6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL-6, and IgE assays were compared between PTLD cases and non-cases at <3, 3-6 and >6 months after transplantation. Median IL-6 levels in PTLD cases were 15.5 (2.0-87.1) and 23.3 (2.1-276) pg/mL compared with 3.25 (0.92-114) and 3.5 (0.75-199.25) pg/mL in non-cases at 3-6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL-6 levels correlated with VL and PTLD occurrence (Spearman's coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL-6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL-6 levels can improve the clinician's ability to identify PTLD, among patients with elevated EBV viral loads.

Incidence of infective endocarditis and its thromboembolic complications in a pediatric population over 30years.

BACKGROUND: Pediatric infective endocarditis (IE) has been associated with high morbidity and mortality, mostly related to thromboembolic complications (TEC). The objective of our study was to describe the experience in children with IE and to review the changes over a thirty-year period, regarding origin of IE, incidence of vegetations, TEC and their respective morbidity and mortality rates. METHODS: A retrospective chart review of children aged 0-18years with IE defined by the Duke Criteria and admitted to The Hospital for Sick Children, was conducted. Data were divided into three periods (P); P1 (1979-1988); P2 (1989-1998); and P3 (1999-2008). RESULTS: The study included 113 patients, median age 7yrs.; females: 46 (41%), congenital heart defects 95 (84%), comparable in all periods. Overall, cardiac vegetations were found in 68/113 patients (60%); large vegetations (≥1cm) in 32 patients (28%). Fourty-five (45/133 [40%]) TEC were documented, 22 patients (20%) developed cerebrovascular events (CVE) and 23 patients (20%) had non-CVE. Patients diagnosed during P3 were older, had more vegetations (p<0.05), and a higher incidence of community acquired-IE (p<0.05). Overall, mortality was 15%, comparable in all periods. Significant risk factors for mortality were vegetations (HR 6.44; 95% CI: 2.07-20.01, p=0.002) and heart failure (HR 28.39; 95% CI: 10.49-76.85, p<0.001). CONCLUSIONS: Over the study period, we report a growing incidence of community acquired pediatric IE in older children accompanied by an increasing rate of TEC. Heart failure and vegetations were associated with an increased mortality. These preliminary data need to be confirmed by prospective data.

Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.

Percutaneous injuries among health care workers. The real value of human immunodeficiency virus testing of 'donor' blood.

A decision analysis was conducted to examine whether health care workers should receive short-term (42 days) zidovudine treatment following percutaneous exposure to blood, as well as to determine the value of testing "donor" (patient's) blood. Three alternative options were analyzed: treat all, treat none, and test. In the treat all option, all health care workers receive short-term zidovudine therapy immediately after exposure; in the treat none option, no one receives zidovudine; and in the test option, donor blood is tested, and if it is human immunodeficiency virus (HIV) positive, zidovudine is given. Baseline variables were obtained from the literature. Each outcome was expressed as a utility; this is a method of quantifying the values that persons place on different health states. The results showed that the test option was preferred. Sensitivity analyses indicated that even if the risk of seroconversion were zero or the effectiveness of zidovudine were zero or the drug were withheld, this option was preferred, thus indicating some value of testing other than merely identifying health care workers who should receive zidovudine. In the baseline analysis, this was derived from the fact that approximately 95% of the health care workers would be reassured by a negative test; ie, only approximately 5% of donors are HIV positive. If the prevalence of HIV seropositivity exceeded 42%, the treat none option was preferred. This was found to be due to the fact that increased numbers of health care workers would be told that they were exposed to HIV-positive blood. The "worrying factor" associated with such an exposure was such that above 42% HIV seropositivity, the treat none option was preferred overall. Thus, the real value of testing donor blood is in identifying those persons (greater than 95%) who could be told that they were exposed to HIV-negative blood, that is, reducing their worrying factor to zero. Because acquired immunodeficiency syndrome is a fatal disease, and given that zidovudine is the only available therapeutic option at present, the drug has an important role to play if its effectiveness is greater than zero.

Serum immunoreactive erythropoietin levels and associated factors amongst HIV-infected children.

OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged < 13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radioimmunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: The study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/l, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.01 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.

Lymphoproliferative disorders after organ transplantation in children.

BACKGROUND: After organ transplant, patients are at risk of posttransplant lymphoproliferative disorders (PTLD). The purpose of this study was to analyze 26 pediatric cases of PTLD observed at our institution between 1988 and 1996, and to evaluate the validity of the Society for Hematopathology Workshop (SHPW) 1997 classification in our patient population. METHODS: Charts were reviewed for analysis of incidence, clinical course, and outcome. Tissue samples were classified by a pathologist according to SHPW recommendations. RESULTS: By morphology, 20 were monomorphic, 5 polymorphic, and 1 hyperplastic. Assessment of lineage by morphology, molecular studies, and immunophenotyping did not correlate in six cases. By immunophenotyping, 12 were B cell, 4 T cell, 8 mixed B/T cells, and 2 undetermined. The 20 patients evaluable for treatment efficacy were treated with various therapeutic combinations, including immunosuppressive drug reduction, acyclovir/ganciclovir, interferon-alpha, immunoglobulins, surgery, and local irradiation. No patient received systemic chemotherapy. Thirteen patients achieved complete remission and 3, partial; 1 died 5 days after starting therapy, and 3 of progressive disease. Adverse prognostic factors included low platelet or neutrophil counts; stage III-IV and SHPW morphology were marginally significant. CONCLUSIONS: The majority of patients eligible for treatment can be cured with immunosuppressive drug reduction and antiviral drugs, along with surgery and irradiation when indicated. Systemic chemotherapy or innovative approaches may have a role in unresponsive cases. Morphologic SHPW grouping is feasible and seems to have clinical relevance. However, correlation with clonality and immunophenotyping is not always possible, necessitating modifications including segregation of descriptive morphology from clonality and cell origin.

Epidemiologic study of 4684 hospital-acquired infections in pediatric patients.

During a 4-year period 4684 nosocomial infections occurred in a university pediatric hospital which admitted 78,120 patients (nosocomial infection rate (NIR) = 6.0). NIR varied from 0.17 to 14.0 on different wards or services; the highest rates (greater than or equal to 5.6) were found in the Neonatal Intensive Care Unit, infant neurosurgery, hematology/oncology, neonatal surgery, cardiology/cardiovascular surgery, Pediatric Intensive Care Unit and infant/toddler medicine areas. Infections were most common in patients less than or equal to 23 months (NIR = 11.5), were less common in the 2- to 4-year age group (NIR = 3.6) and occurred least frequently in patients greater than or equal to 5 years (NIR = 2.6). The median day of onset of infections was 15.3 days. The proportional frequencies of infections were: 35% gastrointestinal; 21% bacteremia; 16% respiratory (10% upper, 6% lower); 7% postoperative wound; 6% urinary tract; 5% skin (32% of these skin infections were related to intravascular lines); 5% eye; 3% cerebrospinal fluid; and 2% other. A similar proportional frequency of 379 infections in patients hospitalized for more than 100 days was observed. The etiologic agents were Gram-positive bacteria (50%), viruses (23%), Gram-negative bacteria (18%), fungi (4%) and mixed/other (5%).

Viridans streptococcal septicaemia in neutropenic patients: role of proinflammatory cytokines.

The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1beta, IL8, and TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.

The utility of plasma polymerase chain reaction for human herpes virus-6 among pediatric bone marrow transplant recipients: results of a pilot study.

We evaluated the utility of plasma polymerase chain reaction (PCR) for surveillance of human herpes virus 6 (HHV-6) infection among pediatric bone marrow transplant (BMT) recipients. We used a prospective, non-interventional design involving a study group and controls. BMT recipients and healthy controls were evaluated. BMT subjects had HHV-6 PCR done biweekly for 12 weeks post transplantation, while a single PCR test was done on controls. For the PCR assay, EDTA blood was collected and DNA extracted from whole blood and cell-free plasma using standard procedures. The PCR was first performed on DNA from whole blood and if a positive result was obtained, the test was repeated on the DNA from the plasma. Thirty BMT recipients (13 autologous and 17 allogeneic) were enrolled, on whom a total of 156 PCR tests were performed, while six tests were done on six healthy controls. The median age of BMT subjects was 6.2 years (range 0.5-17.5 years). The median age of the control subjects was 6.6 years (range 2-10 years). Among asymptomatic BMT patients who had PCR surveillance, the positivity rate was 3.3% (1/30) on whole blood and 0% (0/30) on plasma. None of the six healthy subjects had a positive PCR test on whole blood. During the period of the surveillance study, 14 patients had diagnostic evaluations for HHV-6 disease because of clinical symptoms. Two of these patients were diagnosed with disease associated with HHV-6 (graft failure and encephalitis) and had positive PCR tests on whole blood and plasma and whole blood and cerebrospinal fluid, respectively. We conclude that despite the fact that HHV-6 seropositivity rates are high among children, the frequency of HHV-6 plasma PCR positivity is low in pediatric BMT subjects who are asymptomatic for HHV-6 disease. Given that a positive test on plasma is consistent with active infection, this increases the utility of the PCR test as a diagnostic aid in evaluating syndromes presumed to be due to HHV-6 in pediatric bone marrow transplant recipients.

Nosocomial infections in the pediatric patient: an update.

Substantial progress has been made in measuring the burden of nosocomial infection in pediatric patients, particularly in certain populations (e.g., critical care, immunocompromised, chronic care, and patients with acquired immunodeficiency syndrome) and after certain procedures (e.g., central catheter lines and open-sternum cardiovascular surgery). Preventive measures, such as the use of goggles, gowns, and gloves, have been subjected to new and additional study. The following report is a summary of recent progress. A review of factors responsible for infection in various patient care populations and settings and recommendations for control are presented.

Canadian national survey of perinatal HIV infection 1991-1992. Canadian Paediatric AIDS Research Group (CPAR).

OBJECTIVE: To define the burden of illness and the demographic characteristics of perinatally HIV exposed children in Canada. METHODS: Two national surveys of children born to HIV-infected mothers were conducted. The first survey captured information on all known cases up to March 1991, and the second, additional cases between April 1991 and May 1992. RESULTS: 220 children born to 204 HIV-infected mothers were identified. Quebec cases increased by 20% compared with 33% in Ontario (p < .003) and 50% in the rest of the country (p < .001). Quebec has a higher proportion of black mothers than the rest of Canada (p < .001). Sexual contact continues to be the major risk factor for maternal HIV infection. CONCLUSIONS: This survey confirms a substantial case load and provides an initial demographic profile of diagnosed HIV exposed infants in Canada.

Cephalhematomas revisited. When should a diagnostic tap be performed?

The purpose of this article is to review the most appropriate method for investigating cephalhematomas for possible infection and to clarify the indications for diagnostic aspiration. MEDLINE searches were conducted for the period from 1972 to 1993, and all English-language reports were obtained. A summary of the findings from the reports identified was supplemented by a patient report. Eleven articles reporting 13 infected cephalhematomas were identified in the literature from 1972 to 1993. Escherichia coli was isolated from approximately 50% of the cephalhematomas that were aspirated. Most patients presented with obvious clinical signs of scalp infection, sepsis, meningitis, and/or osteomyelitis. Plain radiographs, bone scans, and enhanced CT scans were limited in their ability to determine if a cephalhematoma was infected unless associated osteomyelitis existed. Aspiration is the diagnostic procedure of choice for cephalhematomas suspected of being infected, as indicated by an increase in size, development of erythema, development of fluctuance, relapse of systemic infection, or a delay in the resolution of clinical symptoms of infection.