Juvenile Dermatomyositis: what comes next? Long-term outcomes in childhood myositis from a patient perspective.

BACKGROUND: To describe long-term outcomes in JDM using patient questionnaires and link to longitudinal, prospectively collected data for each patient within the Juvenile Dermatomyositis Cohort and Biomarker Study, UK and Ireland (JDCBS) to determine outcome predictors.  METHODS: JDCBS participants aged ≥ 16y completed the SF36, HAQ and a questionnaire regarding current disease features, medications, education and employment. Data collected from the JDCBS included disease subtype, demographics, clinical and laboratory features. Intensity indices were calculated for physician VAS, modified skin DAS, CMAS and MMT8 by dividing area under the curve (AUC) from longitudinal score trajectories by duration of study follow-up (y). Relationships between questionnaire and JDCBS clinical / laboratory data were investigated fitting statistical models appropriate for cross sectional and longitudinal data. RESULTS: Of 190 questionnaires sent, 84 (44%) were returned. Average age of respondents was 20.6 years (SD 3.9), time since diagnosis was 12.4 years (SD 5.0), age at onset was 9.2 years (SD 4.3), female to male ratio 4.25:1. Forty-nine (59%) self-reported persistently active disease, 54 (65%) were still taking immunosuppressive medication. 14/32 at school/higher education reported myositis adversely affecting academic results. 18-24 year-olds were twice as likely to be unemployed compared the UK population (OR = 0.456, 95% CI 0.24, 0.84, p = 0.001). Participants ≥ 18 years were three times as likely to be living with a parent/guardian (OR = 3.39, p < 0.001). SF36 MCS and MMT8 intensity index scores were significantly correlated (ρ = 0.328, p = 0.007). CONCLUSIONS: After 12.4 years, questionnaire responders reported self-perceived high rates of persistently active disease and medication use, reduced rates of employment and were more likely to live with a parent/guardian. Perceived persistently active muscle disease appeared to affect quality of life in these patients and was the most significant contributor to long-term outcomes. Our findings highlight the importance of including the patient perspective in the assessment of long term outcomes, so that that we can start to target initial management strategies more effectively based on a combination of clinical and patient-reported data.

Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunizations.

Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous 5 y or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare provider (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p < 0.001) and influenza vaccine (RR 2.26, p = 0.001). Non-English speaking mothers were significantly less likely to have received pertussis vaccination prior to pregnancy or postnatally (RR 0.24, p = 0.011). Multiparous pregnant women were less likely to have received an influenza vaccine during their current pregnancy (p = 0.015). Uptake of pregnancy related immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages.

The national incidence and clinical picture of SLE in children in Australia - a report from the Australian Paediatric Surveillance Unit.

OBJECTIVES: The objectives of this paper are to prospectively determine the incidence of paediatric systemic lupus erythematosus (pSLE) in Australia as well as describe the demographics, clinical presentation and one-year outcome. STUDY DESIGN: Newly diagnosed cases of pSLE were ascertained prospectively from October 2009 to October 2011 through the Australian Paediatric Surveillance Unit (a national monthly surveillance scheme for notification of childhood rare diseases) as well as national subspecialty groups. Questionnaires were sent to notifying physicians at presentation and at one year. RESULTS: The annual incidence rate was 0.32 per 10(5) children aged less than 16 years. The incidence was significantly higher in children of Asian or Australian Aboriginal and Torres Strait Islander parents. Approximately one-third of children underwent a renal biopsy at presentation and 7% required dialysis initially although only one child had end-stage kidney disease (ESKD) at one-year follow-up. CONCLUSION: The incidence of pSLE in Australia is comparable to that worldwide with a significantly higher incidence seen in children of Asian and Australian Aboriginal and Torres Strait Islander backgrounds. Renal involvement is common but progression to ESKD, at least in the short term, is rare.

Early determinants of atherosclerosis in paediatric systemic lupus erythematosus.

OBJECTIVES: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE). METHODS: Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies. RESULTS: The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001). CONCLUSIONS: An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.

[A comparison between systolic pressure variations under mechanical ventilation and classic pressure parameters in predicting fluid responsiveness in patients after coronary surgery]. / Studiu comparativ intre variatiile presiunii arteriale sistolice si parametrii presionali clasici in predictia raspunsului hemodinamic la umplere la pacientii post by-pass aorto-coronarian.

Evaluation of the value of the systolic pressure variations (SPV) under mechanical ventilation and of its components (delta down and delta up) in predicting fluid responsiveness in patients after coronary surgery by comparison with classic parameters. A prospective,randomized study, on 50 patients who underwent CABG surgery, in the early postoperative period (the first two hours). We assessed the following parameters: CO, CI, CVP, PCWP, SAP, DAP, MAP, SVP, delta down and delta up. The including criteria were: sinus rhythm, CI < or = 2,5 l/min/m2, PCP < 18 mmHg. All the patients underwent a fluid challenge (500 ml of colloids in 10 min). Three patients were excluded: 3 for a PCWP > 18 mm Hg, 1 for loosing the sinus rhythm and 1 for an early return in the OR for bleeding. After a new assessment of the same parameters the patients were divided in two groups: group A (28 pts) with a raise of CI > 15%, and group B (22 pts) with a CI variation < 15%. In each group was statistically analyzed the variation of each parameter. Results Both parameters provided by SPV analysis are able to predict the fluid responsiveness with a great accuracy: the positive predictive value of a SPV > 12 mmHg is above 92,85% and of a delta down > 5 mm Hg is above 96,42%; the negative predictive value of a SPV < or = 12 mmHg is above 90,90% and of a delta down = 5 mm Hg is above 95,45%. None of the "classic" pressure parameters (MAP, CVP, PCWP) used in hemodynamic assessment have revealed a statistical significant variation. The SVP method's parameters are superior to classic pressure parameters (MAP, CVP, PCWP) in predicting fluid responsiveness in patients after coronary surgery.

Developmental immunology and vaccines: immune responses to vaccines in premature infants.

A comparatively small number of studies have assessed the safety, immunogenicity, efficacy and duration of immune responses in preterm infants compared with term infants for routinely recommended childhood immunizations.

Storage at -3 degrees C for 24 h alters the immunogenicity of pertussis vaccines.

The immunogenicity of pertussis antigens in an acellular and a whole-cell triple antigen vaccine used for childhood immunisation was assessed in murine models after storage of vaccines below 0 degree C. Swiss outbred and Balb/c mice received DTPa or DTPw vaccine or placebo. Vaccines were stored at 2-8 degrees C (ideal), or at -3 degrees C for 24 h. Pre and post immunisation IgG responses to pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) were measured using enzyme immunoassays (EIA). In Balb/c mice, responses to pertactin after receiving adversely stored DTPa were significantly reduced (P = 0.005, difference in GMCs 145.9% [24.6-385.4%]). A reduction in GMC to pertactin was also seen in response to adversely stored DTPw (P = 0.190,224.1% [83.8-599.2%]). Outbred mice receiving adversely stored DTPa had lower IgG antibody responses to FHA than those receiving correctly stored vaccine (P = 0.002,522.2% [26.1-2155.6%]). Outbred mice also had a significantly lower response to FHA after administration of DTPw (P = 0.009,14.0% [3.8-51.9%]). Responses to DTPa in both strains generally were greater than those to DTPw. Storage of pertussis vaccines below 0 degree C appears to alter the immunogenicity of PRN and FHA. Further study is required to determine the effects of such storage on vaccine protective efficacy.

Parent reported allergy and anaphylaxis in 4173 South Australian children.

OBJECTIVES: To determine the prevalence of parent reported allergy and anaphylaxis in a sample of children and to investigate the first aid management of anaphylaxis in the schools and preschools that these children attend. METHODS: The study sample comprised 4173 South Australian children aged 3-17 years. Information was collected regarding parent-reported allergy and anaphylaxis. All children with known anaphylaxis were contacted and an attempt was made to contact those with reports of allergy to ascertain if these children had anaphylaxis. A telephone questionnaire was used to verify reports of anaphylaxis and determine the cause, severity and school first aid management of anaphylaxis. RESULTS: The rate of parent reported allergy and anaphylaxis was 7.3 and 0.59 per 100 children, respectively. Two-thirds of children with anaphylaxis did not have emergency medication available at school, an emergency action plan, or a teacher on site able to administer adrenaline for first aid use. CONCLUSIONS: Children attending preschool or school may have had a past history of anaphylaxis. Arrangements for first aid management of these children while in this environment are often inadequate.

Cannabis cookies: a cause of coma.

Despite the prevalence of cannabis use in the community, reports of adverse effects in young children are rare. Two cases of cannabis-induced coma are reported following accidental ingestion of cannabis cookies. The possibility of cannabis ingestion should be considered in cases of unexplained coma in a previously well young child if signs of conjunctival hyperaemia, pupillary dilatation and tachycardia are present and other causes such as CNS infection or trauma are unlikely. Specific screening for cannabinoids should be undertaken.

Comparison of balanol from Verticillium balanoides and ophiocordin from Cordyceps ophioglossoides.

Recently, we reported the isolation of the potent protein kinase C inhibitor balanol (1) from the fungus Verticillium balanoides. In an earlier study, König et al. reported the isolation of ophiocordin (3), a structural isomer of 1, from the fungus Cordyceps ophioglossoides. The present study was designed to clarify whether or not balanol and ophiocordin are different compounds. The results indicated that the two fungi produced the same compound, the structure being that assigned to balanol. In addition, a thirty-fold increase in the production of balanol from V. balanoides was observed when the culture medium was changed from cornmeal/tomato paste to soy meal/glycerol.

Processing of iridoid glycoside antirrinoside fromMaurandya antirrhiniflora (Scrophulariaceae) byMeris paradoxa (Geometridae) andLepipolys species (Noctuidae).

The iridoid glycoside antirrinoside was found to be sequestered by highly aposematic larvae of the geometrid mothMeris paradoxa and two noctuid mothLepipolys species feeding onMaurandya antirrhiniflora (Scrophulariaceae), a natural food plant from southern Arizona. The antirrinoside content of leaves and petioles being consumed, eariy-instar larvae, late-instar larvae, larval frass, regurgitant, reflex-bleeding emission (Meris paradoxa), cocoons, pupae, meconium emitted upon eclosion, and adult moths was determined. Larvae, other than the earliest instars, did not excrete antirrinoside in the frass, but sequestered it in amounts of 3-11 % of the dry weight. Small amounts of antirrinoside remained in various pupal or cocoon parts and some was emitted in the meconium upon eclosion. The total antirrinoside accounted for was, however, considerably below that expected based upon the remarkably high 20% content of the leaves and petioles being consumed. The adult cryptic moths of both species contained little or no antirrinoside. This is the first report of a natural food plant and larval stages forM. paradoxa and a previously undescribedLepipolys species. It is also the first report of antirrinoside sequestration and utilization by insects.