Pediatrics Fifth Disease or Erythema Infectiosum Publications (1558)
Pediatrics Fifth Disease or Erythema Infectiosum Publications
We searched the Cochrane Kidney and Transplant Specialised Register to 12 September 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
We included randomised control trials (RCTs) comparing different frequencies, routes, doses and types of short-acting ESAs in CKD patients.
Two authors independently assessed study eligibility and four authors assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.
We identified 14 RCTs (2616 participants); nine studies were multi-centre and two studies involved children. The risk of bias was high in most studies; only three studies demonstrated adequate random sequence generation and only two studies were at low risk of bias for allocation concealment. Blinding of participants and personnel was at low risk of bias in one study. Blinding of outcome assessment was judged at low risk in 13 studies as the outcome measures were reported as laboratory results and therefore unlikely to be influenced by blinding. Attrition bias was at low risk of bias in eight studies while selective reporting was at low risk in six included studies.Four interventions were compared: epoetin alpha or beta at different frequencies using the same total dose (six studies); epoetin alpha at the same frequency and different total doses (two studies); epoetin alpha administered intravenously versus subcutaneous administration (one study); epoetin alpha or beta versus other epoetins or biosimilars (five studies). One study compared both different frequencies of epoetin alpha at the same total dose and at the same frequency using different total doses.Data from only 7/14 studies could be included in our meta-analyses. There were no significant differences in final haemoglobin (Hb) levels when dosing every two weeks was compared with weekly dosing (4 studies, 785 participants: MD -0.20 g/dL, 95% CI -0.33 to -0.07), when four weekly dosing was compared with two weekly dosing (three studies, 671 participants: MD -0.16 g/dL, 95% CI -0.43 to 0.10) or when different total doses were administered at the same frequency (four weekly administration: one study, 144 participants: MD 0.17 g/dL 95% CI -0.19 to 0.53).Five studies evaluated different interventions. One study compared epoetin theta with epoetin alpha and found no significant differences in Hb levels (288 participants: MD -0.02 g/dL, 95% CI -0.25 to 0.21). One study found significantly higher pain scores with subcutaneous epoetin alpha compared with epoetin beta. Two studies (165 participants) compared epoetin delta with epoetin alpha, with no results available since the pharmaceutical company withdrew epoetin delta for commercial reasons. The fifth study comparing the biosimilar HX575 with epoetin alpha was stopped after patients receiving HX575 subcutaneously developed anti-epoetin antibodies and no results were available.Adverse events were poorly reported in all studies and did not differ significantly within comparisons. Mortality was only detailed adequately in four studies and only one study included quality of life data.
Epoetin alpha given at higher doses for extended intervals (two or four weekly) is non-inferior to more frequent dosing intervals in maintaining final Hb levels with no significant differences in adverse effects in non-dialysed CKD patients. However the data are of low methodological quality so that differences in efficacy and safety cannot be excluded. Further large, well designed, RCTs with patient-centred outcomes are required to assess the safety and efficacy of large doses of the shorter acting ESAs, including biosimilars of epoetin alpha, administered less frequently compared with more frequent administration of smaller doses in children and adults with CKD not on dialysis.
Miliary patterns are the most common findings in the chest X-rays of many infants with congenital TB. In this case, an 18-day-old boy had jaundice on the fifth day of birth, and fever and respiratory distress appeared on the 18th day. Chest X-ray showed diffuse fine bilateral infiltration. Clinically, pneumonia or sepsis was suspected. Respiratory symptoms and chest X-ray findings worsened despite empirical antibiotic therapy. The lungs showed miliary infiltration suggestive of TB. Gastric aspirates were positive for M. tuberculosis. Respiratory distress and fever were gradually improved after anti-TB medication. Congenital TB is difficult to detect because of minimal or no symptoms during pregnancy and nonspecific symptoms in neonates. Hence, clinicians should suspect the possibility of TB infection even if neonates have non-specific symptoms. Early diagnosis and meticulous treatment are required for the survival of neonates with TB.
In the present study, we tried to detect early chronic kidney diseases (CKD) among BL survivors by using novel screening modalities.
we investigated 53 children (aged 10 ± 2.8 years, 34 boys) who successfully treated for Burkitt lymphoma, based on LMB96 protocol, as "patient group" and 30 children as control. All eligible participants were subjected to history taking, physical assessment, and routine laboratory investigations including urine analysis, serum creatinine. Estimated glomerular filtration rates using new Schwartz formula (GFRCKD) were calculated and chronic kidney disease prevalence was diagnosed accordingly. Also, serum Cystatin-C (Cys-C) and neutrophil-gelatinase-associated Lipocalin (NGAL) were determined as novel markers aiming at early and accurate detection of CKD in BL survivors.
After 18.3 ± 5.2 months of BL cytotoxic therapy completion, almost one fifth of asymptomatic BL survivors showed evidence of subclinical CKD when estimated GFRCKD (16.9%), serum Cystatin-C (15%) and serum neutrophil-gelatinase-associated Lipocalin (18.8%) were used for kidney function monitoring. This prevalence was four to fivefolds higher than that detected by routine serum creatinine screening (3.7%). Significant persistent albuminuria was diagnosed at 4/53 (7.5.3%) of BL survivors and asymptomatic hypertension was reported in 1/53 (1.9%) of them compared to none of the controls. Positive correlation could be displayed between serum Cys-C and serum NGAL. Conversely, negative correlations between both of them and estimated GFRCKD were documented.
Novel modalities such new Schwartz formula (GFRCKD) estimation, serum Cys-C, and serum NGAL assessment should be incorporated in the routine follow-up screening for CKD among BL survivors for accurate diagnosis of such detrimental morbidity.
Statin drugs have helped to improve the biochemical profile and life expectancy in HeFH, while they are only minimally effective in HoFH. LDL apheresis remains an effective treatment option in HoFH, though limited by its availability and affordability issues. We present the case that highlights a few novel aspects of clinical and genetic heterogeneity in FH, wherein a child presented with features of both HeFH and HoFH. His clinical picture was that of HoFH; however he responded well clinically and biochemically to pharmacologic treatment only. DNA sequencing showed a novel heterozygous rare splicing variant in the LDLR gene in addition to a relatively high polygenic trait score comprised of LDL-C raising alleles from common polymorphic sites. Interestingly his normolipemic mother showed the same heterozygous mutation. Thus this novel splicing variant in LDLR showed nonclassical co-segregation with the disease phenotype and was associated with a high polygenic trait score comprised of common LDL-C raising polymorphic alleles in the affected proband. Thus it indicates the phenotypic heterogeneity of FH and suggests that secondary causes, such as polygenic factors and possibly as yet undetermined genetic or environmental factors, can exacerbate the metabolic phenotype in an individual who is genotypically heterozygous for FH.
The phylogenetic tree supported the division of the G1a into two well-defined clades with 1.3% of divergence. The low diversity of the G1a strains may be explained by the fact that all patients had acute B19V infection and 30/32 sera were collected during two distinct outbreaks. The G3b strain was from an HIV-infected patient who seroconverted to anti-B19 IgG antibodies in September/2005. This is the first report of G3b in the state of Rio de Janeiro.
Combining new cell and gene therapy technology is an exciting approach that appears promising in vitro. Animal testing and careful clinical trials will be needed to determine if these strategies are clinically useful.
NS1-nuc was found to bind with high cooperativity and with multiple (five to seven) copies to the NS1 binding elements (NSBE) found in the viral origin of replication and the overlapping viral p6 promoter DNA sequence. NS1-nuc was also found to bind cooperatively with at least three copies to the GC-rich Sp1 binding sites of the human p21 gene promoter. Only weak or nonspecific binding of NS1-nuc to the segments of the TNFα and IL-6 promoters was found. Cleavage of DNA by NS1-nuc occurred at the expected viral sequence (the terminal resolution site), but only in single-stranded DNA, and NS1-nuc was found to covalently attach to the 5' end of the DNA at the cleavage site. Off-target cleavage by NS1-nuc was also identified.
Next, using skin fibroblasts from an individual expressing these variants and HeLa cells with varying degrees of PiC depletion, PiC loss of ∼60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos), whereas lower maximal oxphos was evident at ∼85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete medium; however, proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1 or MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (>85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss of function may be independent of phosphate limitation when ATP requirements are not high.
Despite this rapidly increasing disease burden there is limited evidence on the economic burden of road traffic injuries on households in South Asia. We applied a novel coarsened exact matching method to assess the household economic burden of road traffic injuries using nationally representative World Health Survey data from five South Asian countries- Bangladesh, India, Nepal, Pakistan and Sri Lanka collected during 2002-2003. We examined the impact of road traffic injuries on household out-of-pocket (OOP) health spending, household non-medical consumption expenditure and the employment status of the traffic injury-affected respondent. We exactly matched a household (after 'coarsening') where a respondent reported being involved in a road traffic injury to households where the respondent did not report a road traffic injury on each of multiple observed household characteristics. Our analysis found that road traffic injury-affected households had significantly higher levels of OOP health spending per member (I$0.75, p<0.01), higher OOP spending on drugs per member (I$0.30, p = 0.03), and higher OOP hospital spending per member (I$0.29, p<0.01) in the four weeks preceding the survey. Indicators of "catastrophic spending" were also significantly higher in road traffic injury-affected households: 6.45% (p<0.01) for a threshold of OOP health spending to total household spending ratio of 20%, and 7.40% (p<0.01) for a threshold of OOP health spending to household 'capacity to pay' ratio of 40%. However, no statistically significant effects were observed for household non-medical consumption expenditure, and employment status of the road traffic injury-affected individual. Our analysis points to the need for financial risk protection against the road traffic injury-related OOP health expenditure and a focus on prevention.
To further investigate the role of the RBD in connection with a B19V-unrelated capsid, we chemically coupled the VP1u of B19V to the bacteriophage MS2 capsid and tested the internalization capacity of the bioconjugate on permissive cells. In comparison, we studied the cellular uptake and infection of B19V along the erythroid differentiation. The results showed that the MS2-VP1u bioconjugate mimicked the specific internalization of the native B19V into erythroid precursor cells, which further coincides with the restricted infection profile. The successful mimicry of B19V uptake demonstrates that the RBD in the VP1u is sufficient for the endocytosis of the viral capsid. Furthermore, the recombinant VP1u competed with B19V uptake into permissive cells, thus excluding a significant alternative uptake mechanism by other receptors. Strikingly, the VP1u receptor appeared to be expressed only on erythropoietin-dependent erythroid differentiation stages that also provide the necessary intracellular factors for a productive infection. Taken together, these findings suggest that the VP1u binds to a yet-unknown erythroid-specific cellular receptor and thus restricts the virus entry to permissive cells.