High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins

IntroductionTakayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV.MethodsTwenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay.ResultsIn GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45–2.10) ng/ml vs. 1.46 (0.89–3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63–2.16) ng/ml vs. 0.75 (0.39–2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29–1.46) ng/ml vs. 1.93 (0.88–3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status.ConclusionsPatients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.     

An Assessment of Diversity,Inclusion, and Health Equity Training in Endocrinology Fellowship Programs in the United States

ContextThe Accreditation Council for Graduate Medical Education has instituted common program requirements related to diversity, equity, and inclusion (DEI) for postgraduate trainees in the United States; however, the extent to which DEI training is being incorporated across endocrinology fellowship programs is unknown.ObjectivesTo describe the sociodemographic representation and DEI training experiences within endocrinology fellowship programs.Design, setting, and participantsNational cross-sectional survey study of fellows and fellowship program leaders in the United States whose fellowships were members of the Association of Program Directors in Endocrinology and Metabolism.Main outcome measures(1) Demographics of fellows and program leaders and (2) programs’ experience, confidence, and interest in formal DEI training.ResultsA total of 108 and 106 fellow and faculty responded to the survey, respectively. The majority of fellows and faculty are female. Less than 3% of fellows and 3.7% of faculty identify as Black. More than 90% of fellows/faculty are heterosexual and no respondents identified as transgender/nonbinary; however, 5% and 2% of all respondents preferred not to disclose their sexual orientation and gender identity, respectively. While 85% of faculty received institutional diversity and inclusion training, 67.6% of fellows did. Fellows are more likely to have received training in health equity than program leaders. Both fellows and program leaders express a high interest in health equity curriculum.ConclusionsWithin the diversity of endocrinology training programs, Black physicians are underrepresented in medicine, which persists in endocrinology fellowships. Fellowship programs express enthusiasm for national diversity and health equity curricula, with the majority of programs reporting institutional DEI training.     

Validity of Antibodies in Lymphocyte Supernatant in Diagnosing Tuberculosis in Severely Malnourished Children Presenting with Pneumonia

BackgroundThe diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia.MethodsChildren less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as “confirmed”, “non-confirmed TB” or “not TB”.ResultsAmong 224 children who had ALS analysis, 12 (5.4%) children had microbiologically “confirmed TB”, a further 41 (18%) had clinically diagnosed “non-confirmed TB” and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as “borderline”. These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing “Confirmed TB” to “Not TB” was only 67% (95% CI: 31–91%) and 51% (95% CI: 42–60%), respectively.

Conclusions and Significance

Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.     

A Prognostic Model for Development of Profound Shock among Children Presenting with Dengue Shock Syndrome

PurposeTo identify risk factors and develop a prediction model for the development of profound and recurrent shock amongst children presenting with dengue shock syndrome (DSS)MethodsWe analyzed data from a prospective cohort of children with DSS recruited at the Paediatric Intensive Care Unit of the Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint was “profound DSS”, defined as ≥2 recurrent shock episodes (for subjects presenting in compensated shock), or ≥1 recurrent shock episodes (for subjects presenting initially with decompensated/hypotensive shock), and/or requirement for inotropic support. Recurrent shock was evaluated as a secondary endpoint. Risk factors were pre-defined clinical and laboratory variables collected at the time of presentation with shock. Prognostic model development was based on logistic regression and compared to several alternative approaches.ResultsThe analysis population included 1207 children of whom 222 (18%) progressed to “profound DSS” and 433 (36%) had recurrent shock. Independent risk factors for both endpoints included younger age, earlier presentation, higher pulse rate, higher temperature, higher haematocrit and, for females, worse hemodynamic status at presentation. The final prognostic model for “profound DSS” showed acceptable discrimination (AUC=0.69 for internal validation) and calibration and is presented as a simple score-chart.ConclusionsSeveral risk factors for development of profound or recurrent shock among children presenting with DSS were identified. The score-chart derived from the prognostic models should improve triage and management of children presenting with DSS in dengue-endemic areas.     

Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis

Introduction

Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement.

Methods

A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography.

Results

Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6.

Conclusions

Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.     

Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: pragmatic randomised trial

ObjectivesTo identify which children with acute otitis media are at risk of poor outcome and to assess benefit from antibiotics in these children.DesignSecondary analysis of randomised controlled trial cohort.SettingPrimary care.Participants315 children aged 6 months to 10 years.InterventionImmediate or delayed (taken after 72 hours if necessary) antibiotics.ResultsDistress by day three was more likely in children with high temperature (adjusted odds ratio 4.5, 95% confidence interval 2.3 to 9.0), vomiting (2.6,1.3 to 5.0), and cough (2.0, 1.1 to 3.8) on day one. Night disturbance by day three was more likely with high temperature 2.4 (1.2 to 4.8), vomiting (2.1,1.1 to 4.0), cough (2.3,1.3 to 4.2), and ear discharge (2.1, 1.2 to 3.9). Among the children with high temperature or vomiting, distress by day three was less likely with immediate antibiotics (32% for immediate v 53% for delayed, χ²=4.0; P=0.045, number needed to treat 5) as was night disturbance (26% v 59%, χ²=9.3; P=0.002; number needed to treat 3). In children without higher temperature or vomiting, immediate antibiotics made little difference to distress by day three (15% v 19%, χ²=0.74; P=0.39) or night disturbance (20% v 27%, χ²=1.6; P=0.20). Addition of cough did not significantly improve prediction of benefit.ConclusionIn children with otitis media but without fever and vomiting antibiotic treatment has little benefit and a poor outcome is unlikely.

What is already known on this topic

Most children with otitis media will not benefit symptomatically from immediate use of antibioticsIt is unclear which children are more likely to benefit from antibiotics and which features predict poor outcome

What this study adds

Children with high temperature or vomiting were more likely to be distressed or have night disturbance three days after seeing the doctorChildren with high temperature or vomiting were more likely to benefit from antibiotics, although it is still reasonable to wait 24-48 hours as many children will settle anywayChildren without high temperature or vomiting were unlikely to have poor outcome and unlikely to benefit from immediate antibiotics     

Delayed Contrast-Enhanced MRI of the Coronary Artery Wall in Takayasu Arteritis

Background

Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD.

Methods

We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34–45 minutes after low-dose gadolinium administration.

Results

No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474).

Conclusion

Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.     

<Emphasis Type="Italic">PVAS3</Emphasis>, a class-II ubiquitous asparagine synthetase from the common bean (<Emphasis Type="Italic">Phaseolus vulgaris)</Emphasis>

A gene encoding a putative asparagine synthetase (AS; EC 6.3.5.4) has been isolated from common bean (Phaseolus vulgaris). A 2.4 kb cDNA clone of this gene (PVAS3) encodes a protein of 570 amino acids with a predicted molecular mass of 64,678 Da, an isoelectric point of 6.45, and a net charge of −5.9 at pH 7.0. The PVAS3 protein sequence conserves all the amino acid residues that are essential for glutamine-dependent AS, and PVAS3 complemented an E. coli asparagine auxotroph, that demonstrates that it encodes a glutamine-dependent AS. PVAS3 displayed significant similarity to other AS. It showed the highest similarity to soybean SAS3 (92.9% identity), rice AS (73.7% identity), Arabidopsis ASN2 (73.2%) and sunflower HAS2 (72.9%). A phylogenetic analysis revealed that PVAS3 belongs to class-II asparagine synthetases. Expression analysis by real-time RT-PCR revealed that PVAS3 is expressed ubiquitously and is not repressed by light.     

Associated factors of the co-occurrence of trachoma and soil-transmitted helminthiases in children 1 to 9 years old in rural communities of the Amazon basin in Loreto Department,Peru: Results from a population-based survey

BackgroundThere is evidence of the occurrence of trachoma in Peru, and studies have shown that soil-transmitted helminthiases (STH) are affecting rural communities in the Amazon basin in Loreto Department. This study was done to estimate trachoma prevalence, STH prevalence, and the associated factors for both diseases in children aged 1–9 years in rural communities of Peru.MethodologyA population-based cross-sectional survey was carried out in rural communities of Loreto. A standardized survey questionnaire with individual and household risk factors related to both diseases was used. Ocular examination was done for all participants aged one year and above, and eye swab samples were collected from children with follicular trachoma (TF). Anthropometric measurements, stool samples for STH, and blood samples for hemoglobin measurement were taken from children.Principal findingsTF prevalence was 7.74% (95% CI 5.08–11.63%), STH prevalence was 49.49% (95% CI 25.00–52.43%), and prevalence of co-occurrence of both diseases was 5.06% (95% CI 2.80–8.98%) in children aged 1–9 years. Being at age 3–8 years old (AOR = 6.76; 95% CI 1.346–33.947), have an unclean face (AOR = 24.64; 95% CI 6.787–89.444), and having been dewormed in the last six months (AOR = 2.47; 95% CI 1.106–5.514), were risk factors of TF. Being a female (AOR = 0.22; 95% CI 0.103–0.457) was associated with decreased odds of TF. Having been dewormed in the last six months (AOR = 0.30; 95% CI 0.139–0.628) was a preventative factor for STH. Risk factors for children with both diseases mirrored the findings for risk factors for individual diseases.ConclusionsNeglected tropical diseases and associated risk factors overlap in communities living in vulnerable conditions in the Amazon basin of Peru. These findings support the need to implement integrated interventions, including mass drug administration, water, sanitation, and hygiene for both diseases in the study area.     

Predictors of severe illness in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a multicentre cohort study

Background:SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in disease severity over time.Methods:We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.Results:Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13–17 years (adjusted risk difference 27.7%, 95% confidence interval [CI] 8.3% to 47.2%), those aged 6–12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI −0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).Interpretation:We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.

Multisystem inflammatory syndrome in children (MIS-C)¹ manifests as immune dysregulation after SARS-CoV-2 infection.² The syndrome has no pathognomonic features. Thus, the diagnostic criteria of the Royal College of Paediatrics and Child Health (RCPCH), the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) differ, but they all include fever, evidence of systemic inflammation and involvement of at least 1 organ or system.³Our primary objective was to assess initial clinical or laboratory features that predict severe illness in MIS-C. We also sought to explore changes in overall disease severity and cardiac involvement over time as it was the impression of many investigators that severity of MIS-C increased through pandemic waves.     

Survival Outcomes in a Pediatric Antiretroviral Treatment Cohort in Southern Malawi

BackgroundPediatric uptake and outcomes in antiretroviral treatment (ART) programmes have lagged behind adult programmes. We describe outcomes from a population-based pediatric ART cohort in rural southern Malawi.MethodsData were analyzed on children who initiated ART from October/2003 –September/2011. Demographics and diagnoses were described and survival analyses conducted to assess the impact of age, presenting features at enrolment, and drug selection.ResultsThe cohort consisted of 2203 children <15 years of age. Age at entry was <1 year for 219 (10%), 1–1.9 years for 343 (16%), 2–4.9 years for 584 (27%), and 5–15 years for 1057 (48%) patients. Initial clinical diagnoses of tuberculosis and wasting were documented for 409 (19%) and 523 (24%) patients, respectively. Median follow-up time was 1.5 years (range 0–8 years), with 3900 patient-years of follow-up. Over the period of observation, 134 patients (6%) died, 1324 (60%) remained in the cohort, 345 (16%) transferred out, and 387 (18%) defaulted. Infants <1 year of age accounted for 19% of deaths, with a 2.7-fold adjusted mortality hazard ratio relative to 5–15 year olds; median time to death was also shorter for infants (60 days) than older children (108 days). Survival analysis demonstrated younger age at ART initiation, more advanced HIV stage, and presence of tuberculosis to each be associated with shorter survival time. Among children <5 years, severe wasting (weight-for-height z-score </ = -3.0) was also associated with reduced survival.ConclusionsCumulative incidence of mortality was 5.2%, 7.1% and 7.7% after 1, 3, and 5 years, respectively, with disproportionate mortality in infants <1 year of age and those presenting with tuberculosis. These findings reinforce the urgent need for early diagnosis and treatment in this population, but also demonstrate that provision of pediatric care in a rural setting can yield outcomes comparable to more resourced urban settings of poor countries.     

Serology,infection, and clinical trachoma as tools in prevalence surveys for re-emergence of trachoma in a formerly hyperendemic district

BackgroundTo eliminate trachoma as a public health problem, countries must achieve a district-level prevalence of trachomatous inflammation—follicular (TF) <5% in children ages 1–9 years. Re-emergence of TF could trigger additional rounds of mass drug/antibiotic administration (MDA), so accurate tools for use in surveys assessing trachoma prevalence are essential.Methodology & principal findingsWe surveyed 2401 children ages 1–9 years from 50 villages in Kongwa, Tanzania, 2 years post-MDA and 1.5 years after an impact survey found TF <5% in the same villages. Our survey included multiple tools: clinical determination of TF, Cepheid testing for Chlamydia trachomatis infection, and testing for anti-pgp3 antibodies via multiplex bead array. Photographs of the upper tarsal conjunctiva were taken in a subset of children to corroborate the field grades.Overall TF prevalence in 1–9 year olds was 7.1% (95% CI: 5.6%-8.9%), which decreased with age (p = <0.0001). TF prevalence by village was heterogeneous, with 19 villages having TF <5% and 16 villages having TF >10%. There was a strong correlation between field and photo grading of TF (kappa = 0.69; 95% CI: 0.60–0.78) and between TF and infection, with 21.5% of TF-positive children also testing positive for infection, as compared to only 1.6% of TF-negative children (p = 0.0010). Overall seroprevalence was 18.2% (95% CI: 14.8%-22.1%), which increased with age (p = <0.0001). Notably, 1–2 year olds, who were born after the cessation of MDA and theoretically should not have had exposure to C. trachomatis in the absence of transmission, had an average seroprevalence of 6.7%.Conclusions & significanceField TF prevalence, supported by photographic review and infection data, suggested re-emergence of trachoma in Kongwa. Moreover, seropositivity in the children born after cessation of MDA indicated exposure to C. trachomatis despite a previous survey finding of TF <5%. Examining seropositivity in specific age groups expected to have limited exposure to C. trachomatis can be used to detect re-emergence.     

Normal Range of Hepatic Fat Fraction on Dual- and Triple-Echo Fat Quantification MR in Children

ObjectivesTo evaluate hepatic fat fraction on dual- and triple-echo gradient-recalled echo MRI sequences in healthy children.ResultsIn 54 children (M:F = 26:28; 5–15 years; mean 9 years), the dual fat fraction (0.1–8.0%; median 1.6%) was not different from the triple fat fraction (0.4–6.5%; median 2.7%) (p = 0.010). The dual- and triple-echo fat fractions showed good agreement using a Bland-Altman plot (-0.6 ± 2.8%). Eight children (14.8%) on dual-echo sequences and six (11.1%) on triple-echo sequences had greater than 5% fat fraction. From these children, six out of eight children on dual-echo sequences and four out of six children on triple-echo sequences had a 5–6% hepatic fat fraction. When using a cut-off value of a 6% fat fraction derived from a reference interval, only 3.7% of children were diagnosed with fatty liver. There was no significant correlation between clinical and laboratory findings with dual and triple-echo fat fractions.ConclusionsDual fat fraction was not different from triple fat fraction. We suggest a cut-off value of a 6% fat fraction is more appropriate for diagnosing fatty liver on both dual- and triple-echo sequences in children.     

Cardiovascular disease,obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort study

BackgroundSome earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC).Methods and findingsThis was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (<37 weeks 0 days) occurred in 7.9% of children born after ART and 4.8% in children born after SC, and 5.7% versus 3.3% had a low birth weight (<2,500 g). Mean (SD) follow-up time was 8.6 (6.2) years for children born after ART and 14.0 (8.6) years for children born after SC. In total, 135 (0.11%), 645 (0.65%), and 18 (0.01%) children born after ART were diagnosed with cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure, or cerebrovascular disease), obesity or type 2 diabetes, respectively. The corresponding values were 10,702 (0.14%), 30,308 (0.74%), and 2,919 (0.04%) for children born after SC. In the unadjusted analysis, children born after ART had a significantly higher risk of any cardiovascular disease (hazard ratio [HR] 1.24; 95% CI 1.04–1.48; p = 0.02), obesity (HR 1.13; 95% CI 1.05–1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08–2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86–1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82–2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06–1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC.ConclusionsIn this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART.Trial registration numberISRCTN11780826.

Emma Norrman and co-workers study the health of children born with and without assisted reproductive technology.     

High prevalence of intestinal parasite infestations among stunted and control children aged 2 to 5 years old in two neighborhoods of Antananarivo,Madagascar

BackgroundThis study aimed to compare the prevalence of intestinal parasite infestations (IPIs) in stunted children, compared to control children, in Ankasina and Andranomanalina Isotry (two disadvantaged neighborhoods of Antananarivo, Madagascar), to characterize associated risk factors and to compare IPI detection by real-time PCR and standard microscopy techniques.Methodology/Principal findingsFecal samples were collected from a total of 410 children (171 stunted and 239 control) aged 2–5 years. A single stool sample per subject was examined by simple merthiolate-iodine-formaldehyde (MIF), Kato-Katz smear and real-time PCR techniques. A total of 96.3% of the children were infested with at least one intestinal parasite. The most prevalent parasites were Giardia intestinalis (79.5%), Ascaris lumbricoides (68.3%) and Trichuris trichiura (68.0%). For all parasites studied, real-time PCR showed higher detection rates compared to microscopy (G. intestinalis [77.6% (n = 318) versus 20.9% (n = 86)], Entamoeba histolytica [15.8% (n = 65) versus 1.9% (n = 8)] and A. lumbricoides [64.1% (n = 263) versus 50.7% (n = 208)]). Among the different variables assessed in the study, age of 4 to 5 years (AOR = 4.61; 95% CI, (1.35–15.77)) and primary and secondary educational level of the mother (AOR = 12.59; 95% CI, (2.76–57.47); AOR = 9.17; 95% CI, (2.12–39.71), respectively) were significantly associated with IPIs. Children drinking untreated water was associated with infestation with G. intestinalis (AOR = 1.85; 95% CI, (1.1–3.09)) and E. histolytica (AOR = 1.9; 95% CI, (1.07–3.38)). E. histolytica was also associated with moderately stunted children (AOR = 0.37; 95% CI, 0.2–0.71). Similarly, children aged between 4 and 5 years (AOR = 3.2; 95% CI (2.04–5.01)) and living on noncemented soil types (AOR = 1.85; 95% CI, (1.18–2.09)) were associated with T. trichiura infestation.Conclusions/SignificanceThe prevalence of IPIs is substantial in the studied areas in both stunted and control children, despite the large-scale drug administration of antiparasitic drugs in the country. This high prevalence of IPIs warrants further investigation. Improved health education, environmental sanitation and quality of water sources should be provided.     

Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study

ObjectiveTo compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of children with prolonged febrile seizures.DesignProspective randomised study.SettingPaediatric emergency department in a general hospital.Subjects47 children aged six months to five years with prolonged febrile seizure (at least 10 minutes) during a 12 month period.InterventionsIntranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg).ResultsIntranasal midazolam and intravenous diazepam were equally effective. Overall, 23 of 26 seizures were controlled with midazolam and 24 out of 26 with diazepam. The mean time from arrival at hospital to starting treatment was significantly shorter in the midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the diazepam group (8.0 (0.5), 7.9 to 8.3). No significant side effects were observed in either group.ConclusionSeizures were controlled more quickly with intravenous diazepam than with intranasal midazolam, although midazolam was as safe and effective as diazepam. The overall time to cessation of seizures after arrival at hospital was faster with intranasal midazolam than with intravenous diazepam. The intranasal route can possibly be used not only in medical centres but in general practice and, with appropriate instructions, by families of children with recurrent febrile seizures at home.     

The Effect of UGT1A1 Promoter Polymorphism in the Development of Hyperbilirubinemia and Cholelithiasis in Hemoglobinopathy Patients

Present study was aimed to explore the effect of (TA)_n UGT1A1 gene promoter polymorphism on bilirubin metabolism, bilirubinaemia, predisposition to cholelithiasis and subsequent cholecystectomy, in Sickle-Cell Anemia (SCA) and beta-Thalasemia major (bTH) in Kuwaiti subjects compared to other population. This polymorphism was analyzed and correlated to total bilirubin and cholelithiasis in 270 age, gender, ethnically matched subjects (92 bTH, 116 SCA and 62 Controls) using PCR, dHPLC, fragment analysis and direct sequencing. Four genotypes of UGT1A1 were detected in this study (TA6/6, TA6/7, TA6/8 and TA7/7). (TA)6/8 was found only in four individuals; hence it was not included in the analysis. There was a statistically significant association of genotypes with serum total bilirubin levels in both bTH and SCA groups (p<0.001). Subjects with (TA)7/7 had the highest total serum bilirubin level (178.7±3.5 µmole/l). A significant association was observed between allele (TA)7 and cholelithiasis development (p = 0.0001). The 40%, 67.5% and 100% of SCA with (TA)6/6, (TA)6/7 and (TA)7/7 respectively developed cholelithiasis and were subsequently cholecystectomized. Our results confirm UGT1A1 (TA)7 allele as one of the factors accounting for the hyperbilirubinemia and cholelithiasis observed in SCA and bTH.     

Cluster Survey Evaluation of a Measles Vaccination Campaign in Jharkhand,India, 2012

IntroductionIndia was the last country in the world to implement a two-dose strategy for measles-containing vaccine (MCV) in 2010. As part of measles second-dose introduction, phased measles vaccination campaigns were conducted during 2010–2013, targeting 131 million children 9 months to <10 years of age. We performed a post-campaign coverage survey to estimate measles vaccination coverage in Jharkhand state.MethodsA multi-stage cluster survey was conducted 2 months after the phase 2 measles campaign occurred in 19 of 24 districts of Jharkhand during November 2011–March 2012. Vaccination status of children 9 months to <10 years of age was documented based on vaccination card or mother’s recall. Coverage estimates and 95% confidence intervals (95% CI) for 1,018 children were calculated using survey methods.ResultsIn the Jharkhand phase 2 campaign, MCV coverage among children aged 9 months to <10 years was 61.0% (95% CI: 54.4–67.7%). Significant differences in coverage were observed between rural (65.0%; 95% CI: 56.8–73.2%) and urban areas (45.6%; 95% CI: 37.3–53.9%). Campaign awareness among mothers was low (51.5%), and the most commonly reported reason for non-vaccination was being unaware of the campaign (69.4%). At the end of the campaign, 53.7% (95% CI: 46.5–60.9%) of children 12 months to <10 years of age received ≥2 MCV doses, while a large proportion of children remained under-vaccinated (34.0%, 95% CI: 28.0–40.0%) or unvaccinated (12.3%, 95% CI: 9.3–16.2%).ConclusionsImplementation of the national measles campaign was a significant achievement towards measles elimination in India. In Jharkhand, campaign performance was below the target coverage of ≥90% set by the Government of India, and challenges in disseminating campaign messages were identified. Efforts towards increasing two-dose MCV coverage are needed to achieve the recently adopted measles elimination goal in India and the South-East Asia region.