Adolescent valuation of CARIES-QC-U: a child-centred preference-based measure of dental caries.

OBJECTIVES: This study develops an adolescent value set for a child-centred dental caries-specific measure of oral health-related quality of life (OHRQoL) based upon CARIES-QC (Caries Impacts and Experiences Questionnaire for Children). This study develops a new approach to valuing child health by eliciting adolescent preferences and anchoring these onto the 1-0 full health-dead QALY (quality adjusted life year) scale using ordinal adult preferences. METHODS: Two online surveys were created to elicit preferences for the CARIES-QC classification system. The first comprised best-worst scaling (BWS) tasks for completion by adolescents aged 11-16 years. The second comprised discrete choice experiment tasks with a duration attribute (DCETTO) for completion by adults aged over 18 years. Preferences were modelled using the conditional logit model. Mapping regressions anchored the adolescent BWS data onto the QALY scale using adult DCETTO values, since the BWS survey data alone cannot generate anchored values. RESULTS: 723 adolescents completed the BWS survey and 626 adults completed the DCETTO survey. The samples were representative of UK adolescent and adult populations. Fully consistent and robust models were produced for both BWS and DCETTO data. BWS preferences were mapped onto DCETTO values, resulting utility estimates for each health state defined by the classification system. CONCLUSION: This is the first measure with predetermined scoring based on preferences to be developed specifically for use in child oral health research, and uses a novel technique to generate a value set using adolescent preferences. The estimates can be used to generate QALYs in economic evaluations of interventions to improve children's oral health.

Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial.

Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml-1 ) vs. albumin (5 (2-74 [0-1604]) ng.ml-1 ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.

Everyone else is using it, so why isn't the UK? Silver diamine fluoride for children and young people.

INTRODUCTION: Silver diamine fluoride (SDF) is used to prevent and arrest caries across the globe, particularly in the developing world. Whilst its use in the Western World is increasing, it is not yet routinely used in the United Kingdom, nor is it advocated by our national guidelines. OBJECTIVES: To explore the literature surrounding the use of SDF, and consider the reasons why SDF has not yet been widely adopted in the United Kingdom (UK). DISCUSSION: There is a growing evidence base for the use of SDF for the arrest and prevention of dental caries in the primary and permanent dentition. Potential side effects include staining of carious tooth structure, but in some cases this is acceptable to parents. There is no evidence for the cost effectiveness of SDF, although it may be a reasonably cost-effective option. CONCLUSION: SDF is perhaps not yet widely adopted in the UK due to a perceived parental concern about its staining effect. With a growing evidence base and reportedly higher efficacy than fluoride varnish for caries prevention and arrest, SDF has the potential to play an important role in managing dental disease in children and young people in both primary and secondary care.

A systematic review of the quality and scope of economic evaluations in child oral health research.

BACKGROUND: Economic evaluations provide policy makers with information to facilitate efficient resource allocation. To date, the quality and scope of economic evaluations in the field of child oral health has not been evaluated. Furthermore, whilst the involvement of children in research has been actively encouraged in recent years, the success of this movement in dental health economics has not yet been explored. This review aimed to determine the quality and scope of published economic evaluations applied to children's oral health and to consider the extent of children's involvement. METHODS: The following databases were searched: CINAHL, Cochrane Library, Econlit, EThOS, MEDLINE, NHS EED, OpenGrey, Scopus, Web of Science. Full economic evaluations, relating to any aspect of child oral health, published after 1997 were included and appraised against the Drummond checklist and the Consolidated Health Economic Evaluation Reporting Standards by a team of four calibrated reviewers. Data were also extracted regarding children's involvement and the outcome measures used. RESULTS: Two thousand seven hundred fifteen studies were identified, of which 46 met the inclusion criteria. The majority (n = 38, 82%) were cost-effectiveness studies, with most focusing on the prevention or management of dental caries (n = 42, 91%). One study quantified outcomes in Quality Adjusted Life Years (QALYs), and one study utilised a child-reported outcome measure. The mean percentage of applicable Drummond checklist criteria met by the studies in this review was 48% (median = 50%, range = 0-100%) with key methodological weaknesses noted in relation to discounting of costs and outcomes. The mean percentage of applicable CHEERS criteria met by each study was 77% (median = 83%, range = 33-100%), with limited reporting of conflicts of interest. Children's engagement was largely overlooked. CONCLUSIONS: There is a paucity of high-quality economic evaluations in the field of child oral health. This deficiency could be addressed through the endorsement of standardised economic evaluation guidelines by dental journals. The development of a child-centred utility measure for use in paediatric oral health would enable researchers to quantify outcomes in terms of quality adjusted life years (QALYs) whilst promoting child-centred research.

Caries prevalence, clinical consequences and self-reported pain experienced by children living in the West Bank.

AIM: To investigate both caries prevalence and clinical consequences experienced by deprived children in the West Bank, using a child-centred approach. MATERIALS AND METHODS: Children were invited by their social workers to attend free dental screening sessions held across clinics in the north of the West Bank. Data were collected using the dmft/DMFT and pufa/PUFA indices. Dental pain was reported by children using the Wong-Baker FACES® pain scale. Data were analysed using SPSS Version 22.0. RESULTS: Data were collected for 177 children aged 4 to 18 years. Caries prevalence was 95.5% with only eight children presenting clinically caries-free. The sample had a dmft of 3.88, and DMFT of 3.44. The Care Index was calculated at 0.1 (mft/dmft). Clinical consequences of caries were identified in 64% of the sample, with a mean pufa score of 2.12, and a PUFA score of 0.55. Dental pain was experienced by 45% of children. CONCLUSION: Deprived children living in the West Bank experience high levels of untreated dental caries, with significant clinical consequences and self-reported pain.

Developing and Applying the Propensity Score to Make Causal Inferences: Variable Selection and Stratification.

This Monte Carlo simulation examined the effects of variable selection (combinations of confounders with four patterns of relationships to outcome and assignment to treatment) and number of strata (5, 10, or 20) in propensity score analyses. The focus was on how the variations affected the average effect size compared to quasi-assignment without adjustment for bias. Results indicate that if a propensity score model does not include variables strongly related to both outcome and assignment, not only will bias not decrease, but it may possibly increase. Furthermore, models that include a variable highly related to assignment to treatment but do not also include a variable highly related to the outcome could increase bias. In regards to the number of strata, results varied depending on the propensity score model and sample size. In 75% of the models that resulted in a significant reduction in bias, quintiles outperformed the other stratification schemes. In fact, the richer that the propensity score model was (i.e., including multiple covariates of varying relationships to the outcome and to assignment to treatment), the more likely that the model required fewer strata to balance the covariates. In models without that same richness, additional strata were necessary. Finally, the study suggests that when developing a rich propensity score model with stratification, it is crucial to examine the strata for overlap.

Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34).

INTRODUCTION: The t(6;9)(p23;q34);DEK-NUP214 [t(6;9)] abnormality is found in 0.7-1.8% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FLT3-ITD mutations are detected in t(6;9) patients. The t(6;9) abnormality is associated with poor outcomes. We studied the clinicopathologic and molecular profiles of patients with AML/MDS carrying t(6;9). METHODS: We collected clinical data of nine patients with AML/MDS with isolated t(6;9) (median age = 41 years; male/female = 4/5) and genotyped DNAs using whole exome, Sanger, and targeted sequencing. RESULTS: Our cohort was characterized by frequent multilineage dysplasia (56%), absence of phospho-STAT3/STAT5 expression, presence of myeloid markers (CD13, CD33, CD34, CD117, HLA-DR) with an aberrant expression of CD7, and poor outcome (median survival of 20 months). Although basophilia has been described in association with t(6;9), we observed lack of marrow basophilia in our cohort. Molecularly, 83% (5/6) of patients with AML/MDS with t(6;9) were characterized by at least one somatic mutation. Among them, four patients showed multiple mutations. FLT3-ITD mutations were detected in 33% of patients (2/6); 80% (4/5) of mutant patients died even after hematopoietic stem cell transplantation. CONCLUSION: Our data demonstrated that AML/MDS patients with t(6;9) have diverse molecular mutations regardless of the presence of FLT3 mutations, which may contribute to their poor survival outcomes.

Unusual extrinsic staining following microabrasion in a girl with amelogenesis imperfecta.

BACKGROUND: Developmental defects of enamel (DDE), such as amelogenesis imperfecta (AI), may present with tooth discolouration that is of aesthetic concern to the affected individual. Children and young people with DDE may therefore seek dental interventions to improve their dental appearance. The most commonly employed approaches include microabrasion, bleaching and/or placement of composite resin veneers. CASE REPORT: A 13-year-old girl with hypomature AI requested treatment for the 'marks' on her teeth which were having a negative impact on her social interactions. Clinical examination revealed generalised dense white opacities, and a microabrasion approach was performed on 11, 12 and 13 using a commercial preparation of 6.6 % hydrochloric acid. Concerningly, the girl's father phoned the next day reporting that his daughter's teeth had turned 'orange'. An urgent review revealed that the treated teeth had indeed become an orange colour. Further enquiry found that the patient had eaten a tomato pizza immediately after her dental treatment and this was believed to have caused the severe extrinsic staining. The patient was provided with a 16 % carbamide peroxide preparation for night-time use in a laboratory-made tray. A 2-week review revealed complete resolution of the staining. FOLLOW-UP: Direct composite resin restorations were subsequently provided for the girl's maxillary anterior teeth to achieve an optimal cosmetic result and she has remained pleased with her dental appearance. CONCLUSION: Clinicians should be aware of the potential for extrinsic staining following microabrasion or tooth bleaching. Patients should be advised against consuming coloured food and drink for at least 48 h after their treatment.

Validation of a panel of ADAMTS13 assays for diagnosis of thrombotic thrombocytopenic purpura: activity, functional inhibitor, and autoantibody test.

INTRODUCTION: Quantitation of ADAMTS13 activity, functional inhibitors, and autoantibodies is crucial in diagnosis and management of thrombotic thrombocytopenic purpura. We compared and optimized commercial assay kits and validated a testing panel. METHODS: Citrated plasma specimens from healthy volunteers and residual samples submitted for clinical testing were used in the study. Commercially available ADAMTS13 activity assays including ACTIFLUOR(™) ADAMTS13 (Sekisui Diagnostics, Stamford, CT, USA), LIFECODES ATS-13 (Gen-Probe Inc., San Diego, CA, USA), and TECHNOZYM(®) ADAMTS-13 (Technoclone, Vienna, Austria) were evaluated. Functional inhibitor assays were performed using internally developed mixing protocols. Two autoantibody assays were also evaluated: IMUBIND(®) (Sekisui Diagnostics) and TECHNOZYM(®) ADAMTS-13 INH ELISA kits (Technoclone). RESULTS: A laboratory-developed assay using ACTIFLUOR(™) reagents showed best agreement with the reference method, and full validation showed a reportable range of 5% (LLOQ) to 114% with a reference interval of ≥68%. Both intra- and interassay coefficients of variation were <10%. Inhibitor assays performed with the kits showed 95% overall agreement with the reference method. A modification of the TECHNOZYM(®) autoantibody assay showed 85% overall agreement with the reference method with imprecision approximately 20%. CONCLUSION: ADAMTS13 activity and inhibitor tests using ACTIFLUOR(™) reagents and modified TECHNOZYM(®) autoantibody ELISA showed superior performance compared to the other kits for clinical use in this study.

Parents' Experiences of Toothbrushing with Children: A Qualitative Study.

Globally, dental caries is one of the most prevalent diseases and is more common in children living in deprived areas. Dental caries is preventable, and guidance in the United Kingdom recommends parental supervised brushing (PSB): a collection of behaviors-including twice-daily toothbrushing with fluoridated toothpaste-that should begin upon eruption of the first tooth (approximately 6 to 12 mo of age) and for which children need to be helped or supervised by an adult until at least 7 y of age. The aim of this study was to explore parents' experiences of toothbrushing with their young children and to establish barriers and facilitators to PSB at individual, interpersonal, and environmental levels according to the theoretical domains framework. Qualitative semistructured interviews guided by the framework were conducted with 27 parents of young children (<7 y) in 2 deprived areas of the United Kingdom. Framework analysis was used. Parents were not aware of national guidance concerning their active involvement in toothbrushing; however, they did have detailed knowledge of toothbrushing practices for children, and their intentions were to brush their children's teeth themselves twice every day as part of a family routine. Nonetheless, parents' difficulties experienced in managing their children's challenging behavior and the environmental context of their stressful lives meant that many parents adopted a role of simply reminding their children to brush or watching them brush. As such, the main barriers to PSB among parents living in deprived areas were skills in managing their children's behavior and environmental influences on family life. The results of our study have clear implications for the development of appropriate interventions to address the modifiable barriers to improve parental adoption of PSB. Knowledge Transfer Statement: The results of this study will be used to develop a behavior change intervention to encourage parental supervised brushing. The intervention-which is likely to be delivered through health practitioners rather than dental teams-will be developed to reduce dental caries among young children and will require evaluation in terms of its clinical and cost effectiveness.

Antibacterial effect of the scandium complex of enterochelin. Studies of the mechanism of action.

There is good evidence to show that ferric enterochelin is an essential growth factor for a number of Gram-negative pathogenic bacteria exposed to the host iron binding proteins, transferrin and lactoferrin. Tests of nineteen complexes of enterochelin as potential antibacterial agents showed that only those containing either indium (In3+) or scandium (Sc3+) inhibited bacterial growth. In this study, further evidence is presented which demonstrates a competition between the Sc3+ and Fe3+ complexes. The uptake of both complexes is energy dependent and is also repressed in iron-replete cells. The Sc3+ complex accumulates within the cells at 20% of the rate of the Fe3+ complex. The main components of the ferric enterochelin transport system are required for the transport of the Sc3+ complex although some Sc3+ appears to enter the cell by another route. The accumulation, within the cell, of 14C-labelled enterochelin complexes depends on the growth medium. The relationship of the size of the metal ion to the biological activity of the complex is discussed and possible mechanisms of action of the Sc3+ complex are considered.

Pollen specific cDNA clones from Zea mays.

We have cloned and sequenced four pollen-specific cDNAs. None of the clones are complete at their 5' ends. One of the clones shows significant homology to the tomato fruit-ripening polygalacturonase and to a pollen-specific polygalacturonase from Oenothera. The other three clones have no significant homologies to any reported sequence.

Production of enterochelin by Escherichia coli 0111.

The major neutral iron-transporting compound produced by Escherichia coli 0111/K58/H2 has been isolated from iron-deficient cultures of the organism and compared with the corresponding compound, enterochelin, produced by E. coli K12. The product contained serine and 2,3-dihydroxybenzoic acid and formed a complex with Fe3+. Since the PMR spectra of the products from the two strains were identical, it was concluded that E. coli 0111 also secreted enterochelin under iron-deficient conditions. Although it was not possible to establish the optical configuration of the serine residues in the molecule, the CD spectra of the metal free and Fe3+, complexes were found to be of the same sign and magnitude. The spectra show that metal binding results in considerable conformational changes in the enterochelin molecule. The biological properties of the two compounds appear to be identical as judged by their ability to abolish the bacteriostatic effect of serum on E. coli 0111.

Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron.

Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA splicing machinery are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe(2+) in mutant and WT. Reactive oxygen species and DNA damage were not increased in SF3B1-mutant patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.

Kinetics of single doses of fenbufen in patients with renal insufficiency.

Fenbufen (gamma-oxo[1,1'-biphenyl]-4-butanoic acid) is a nonsteroidal anti-inflammatory analgesic that is metabolized to four major metabolites: gamma-hydroxy [1,1'-biphenyl]-4-butanoic acid (II), [1,1'-biphenyl]-4-acetic acid (III), 4'hydroxy [1,1'-biphenyl]-4-acetic acid (IV), and gamma, 4'-dihydroxy [1, 1'-biphenyl]-4-butanoic acid (V). Fenbufen and metabolites II and III circulate to plasma and are pharmacologically active; metabolites IV and V are normally excreted in urine. Single 800-mg doses of fenbufen were safely administered to 10 healthy subjects and to 16 patients with varying degrees of renal insufficiency. Drug and metabolite concentrations in serum and urine were determined at intervals for 3 days. It was found that renal impairment altered the metabolic pattern of fenbufen. Although t1/2 beta was the same for fenbufen and II, their plasma levels fell. No change was found in the plasma levels of III. There was evidence of moderate cumulation in plasma of the two more polar urinary metabolites (IV, V) corresponding to the degree of renal insufficiency. The total of all five compounds excreted into the urine was diminished. To account for this, either biliary and gastrointestinal excretion increased or there may have been further hepatic biotransformation of the metabolites.

Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV-seropositive homosexual men.

Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors.

Uroepithelial and nephrotubular toxicity in patients receiving ifosfamide/mesna: measurement of urinary N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin.

The effect of three ifosfamide/mesna regimens on urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and beta-2-microglobulin (beta 2 M) was studied. All regimens produced significant increases in these urinary proteins, indicating nephrotubular damage. In regimen A (n = 15), plasma nitrobenzylpyridine (NBP) alkylating activity area under the curve (AUC) on day 1 correlated with the percentage increase above baseline of maximum urinary NAG activity (r2 = 0.538, P = 0.0022) and maximum beta 2 M concentration (r2 = 0.413, P = 0.0097). In regimen B (n = 5), plasma NBP alkylating activity AUC correlated with the percentage increase above baseline of maximum NAG activity (r2 = 0.843, P = 0.03) and beta 2 M (r2 = 0.78, P = 0.046). In these two regimens the renal exposure to ifosfamide metabolites correlated with the increases in urinary NAG and beta 2 M. The relation of these urinary protein abnormalities to longer term effects on renal function with different ifosfamide/mesna schedules requires further study.

Urinary excretion of prednisolone following intravenous administration in humans.

The urinary excretion of prednisolone was studied in eight normal human volunteers (two women and six men) following intravenous (16, 32, 48 and 64 mg) doses. Urine prednisolone concentrations were determined by a high performance thin layer chromatographic method (HPTLC). The overall mean prednisolone elimination half life in urine following all the intravenous doses as determined by the rate and sigma minus plots was 1.13 +/- 0.25 hour. This was independent of dose and shorter than that found in plasma (4.10 +/- 1.00 s.d. hour). The overall mean percentage of dose excreted unchanged in urine was 16.7 +/- 5.8% following all intravenous and oral doses respectively. About 80% of this amount was excreted within the first 4 hours of the intravenous administration. Renal clearance of prednisolone decreased with time by the first order kinetic (r = 0.790) and its overall value following all IV doses was 0.0183 +/- 0.0103 (s.d.) l/h/kg. The metabolic clearance remained constant with increasing doses from 16 to 64 mg (0.0883 +/- 0.0306 s.d. l/h/kg). From this study it was concluded that a definitive account of the renal elimination of prednisolone and its possible metabolites warrant further investigation. The fraction of the dose excreted unchanged was relatively small and variable suggesting that prednisolone elimination occurs mainly by metabolism.

Iron, infection, and the role of bicarbonate.

Ferric iron will not saturate transferrin in Tris buffer, and its use in experimental infections has been criticized. However, in the presence of bicarbonate, as in plasma, saturation occurs rapidly. This is comparable to natural iron overload, and infections.

The role of Eh, pH and iron in the bactericidal power of human plasma.

The bactericidal power of fresh human plasma against Klebsiella pneumoniae and Escherichia coli was extremely sensitive to changes in Eh and pH. At a high Eh (approx. +200 mV) the bacteria were destroyed, but rapid regrowth occurred when the Eh was lowered to approx. -400 mV. Abolition of the bactericidal effect was also produced by adding ferric iron at a high Eh (approx. +200 mV). Lowering the pH to 6.50 reduced or prevented the bactericidal effect. These results are probably related to the availability of iron for bacterial growth, and could be important for understanding the development of infection in injured or diseased tissue.