Child caries management: A randomized controlled trial in dental practice

This multicenter 3-arm, parallel-group, patient-randomized controlled trial compared clinical effectiveness of 3 treatment strategies over 3 y for managing dental caries in primary teeth in UK primary dental care. Participants aged 3 to 7 y with at least 1 primary molar with dentinal carious lesion were randomized across 3 arms (1:1:1 via centrally administered system with variable-length random permuted blocks): C+P, conventional carious lesion management (complete carious tooth tissue removal and restoration placement) with prevention; B+P, biological management (sealing in carious tooth tissue restoratively) with prevention; and PA, prevention alone (diet, plaque removal, fluorides, and fissure sealants). Parents, children, and dentists were not blind to allocated arm. Co–primary outcomes were 1) the proportion of participants with at least 1 episode of dental pain and/or infection and 2) the number of episodes of dental pain and/or infection during follow-up (minimum, 23 mo). In sum, 1,144 participants were randomized (C+P, n = 386; B+P, n = 381; PA, n = 377) by 72 general dental practitioners, of whom 1,058 (C+P, n = 352; B+P, n = 352; PA, n = 354) attended at least 1 study visit and were included in the primary analysis. The median follow-up was 33.8 mo (interquartile range, 23.8 to 36.7). Proportions of participants with at least 1 episode of dental pain and/or infection were as follows: C+P, 42%; B+P, 40%; PA, 45%. There was no evidence of a difference in incidence of dental pain and/or infection when B+P (adjusted risk difference [97.5% CI]: −2% [−10% to 6%]) or PA (4% [−4% to 12%]) was compared with C+P. The mean (SD) number of episodes of dental pain and/or infection were as follows: C+P, 0.62 (0.95); B+P, 0.58 (0.87); and PA, 0.72 (0.98). Superiority could not be concluded for number of episodes between B+P (adjusted incident rate ratio (97.5% CI): 0.95 [0.75 to 1.21]) or PA (1.18 [0.94 to 1.48]) and C+P. In conclusion, there was no evidence of a difference among the 3 treatment approaches for incidence or number of episodes of dental pain and/or infection experienced by these participants with high caries risk and established disease (trial registration: ISRCTN77044005)

The FiCTION dental trial protocol - fillings children's teeth: indicated or not?

Background: There is a lack of evidence for effective management of dental caries (decay) in children’s primary (baby) teeth and an apparent failure of conventional dental restorations (fillings) to prevent dental pain and infection for UK children in Primary Care. UK dental schools’ teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed. However, the evidence base for this is limited in volume and quality, and comes from studies conducted in either secondary care or specialist practices. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been questioned. The FiCTION trial addresses the Health Technology Assessment (HTA) Programme’s commissioning brief and research question “What is the clinical and cost effectiveness of restoration caries in primary teeth, compared to no treatment?” It compares conventional restorations with an intermediate treatment strategy based on the biological (sealing-in) management of caries and with no restorations. Methods/Design: This is a Primary Care-based multi-centre, three-arm, parallel group, patient-randomised controlled trial. Practitioners are recruiting 1461 children, (3–7 years) with at least one primary molar tooth where caries extends into dentine. Children are randomized and treated according to one of three treatment approaches; conventional caries management with best practice prevention, biological management of caries with best practice prevention or best practice prevention alone. Baseline measures and outcome data (at review/treatment during three year follow-up) are assessed through direct reporting, clinical examination including blinded radiograph assessment, and child/parent questionnaires. The primary outcome measure is the incidence of either pain or infection related to dental caries. Secondary outcomes are; incidence of caries in primary and permanent teeth, patient quality of life, cost-effectiveness, acceptability of treatment strategies to patients and parents and their experiences, and dentists’ preferences. Discussion: FiCTION will provide evidence for the most clinically-effective and cost-effective approach to managing caries in children’s primary teeth in Primary Care. This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth. The trial is currently recruiting patients

Examining the effectiveness of different dental recall strategies on maintenance of optimum oral health: the INTERVAL dental recalls randomised controlled trial

Objective To compare the clinical effectiveness of different frequencies of dental recall over a four-year period. Design A multi-centre, parallel-group, randomised controlled trial with blinded clinical outcome assessment. Participants were randomised to receive a dental check-up at six-monthly, 24-monthly or risk-based recall intervals. A two-strata trial design was used, with participants randomised within the 24-month stratum if the recruiting dentist considered them clinically suitable. Participants ineligible for 24-month recall were randomised to a risk-based or six-month recall interval. Setting UK primary dental care. Participants Practices providing NHS care and adults who had received regular dental check-ups. Main outcome measures The percentage of sites with gingival bleeding on probing, oral health-related quality of life (OHRQoL), cost-effectiveness. Results In total, 2,372 participants were recruited from 51 dental practices. Of those, 648 were eligible for the 24-month recall stratum and 1,724 participants were ineligible. There was no evidence of a significant difference in the mean percentage of sites with gingival bleeding on probing between intervention arms in any comparison. For those eligible for 24-month recall stratum: the 24-month versus six-month group had an adjusted mean difference of -0.91%, 95% CI (-5.02%, 3.20%); the 24-month group versus risk-based group had an adjusted mean difference of 0.07%, 95% CI (-3.99%, 4.12%). For the overall sample, the risk-based versus six-month adjusted mean difference was 0.78%, 95% CI (-1.17%, 2.72%). There was no evidence of a difference in OHRQoL (0-56 scale, higher score for poorer OHRQoL) between intervention arms in any comparison. For the overall sample, the risk-based versus six-month effect size was -0.35, 95% CI (-1.02, 0.32). There was no evidence of a clinically meaningful difference between the groups in any comparison in either eligibility stratum for any of the secondary clinical or patient-reported outcomes. Conclusion Over a four-year period, we found no evidence of a difference in oral health for participants allocated to a six-month or a risk-based recall interval, nor between a 24-month, six-month or risk-based recall interval for participants eligible for a 24-month recall. However, patients greatly value and are willing to pay for frequent dental check-ups

Latherin: A Surfactant Protein of Horse Sweat and Saliva

Horses are unusual in producing protein-rich sweat for thermoregulation, a major component of which is latherin, a highly surface-active, non-glycosylated protein. The amino acid sequence of latherin, determined from cDNA analysis, is highly conserved across four geographically dispersed equid species (horse, zebra, onager, ass), and is similar to a family of proteins only found previously in the oral cavity and associated tissues of mammals. Latherin produces a significant reduction in water surface tension at low concentrations (≤1 mg ml−1), and therefore probably acts as a wetting agent to facilitate evaporative cooling through a waterproofed pelt. Neutron reflection experiments indicate that this detergent-like activity is associated with the formation of a dense protein layer, about 10 Å thick, at the air-water interface. However, biophysical characterization (circular dichroism, differential scanning calorimetry) in solution shows that latherin behaves like a typical globular protein, although with unusual intrinsic fluorescence characteristics, suggesting that significant conformational change or unfolding of the protein is required for assembly of the air-water interfacial layer. RT-PCR screening revealed latherin transcripts in horse skin and salivary gland but in no other tissues. Recombinant latherin produced in bacteria was also found to be the target of IgE antibody from horse-allergic subjects. Equids therefore may have adapted an oral/salivary mucosal protein for two purposes peculiar to their lifestyle, namely their need for rapid and efficient heat dissipation and their specialisation for masticating and processing large quantities of dry food material

Random effects diagonal metric multidimensional scaling models

By assuming a distribution for the subject weights in a diagonal metric (INDSCAL) multidimensional scaling model, the subject weights become random effects. Including random effects in multidimensional scaling models offers several advantages over traditional diagonal metric models such as those fitted by the INDSCAL, ALSCAL, and other multidimensional scaling programs. Unlike traditional models, the number of parameters does not increase with the number of subjects, and, because the distribution of the subject weights is modeled, the construction of linear models of the subject weights and the testing of those models is immediate. Here we define a random effects diagonal metric multidimensional scaling model, give computational algorithms, describe our experiences with these algorithms, and provide an example illustrating the use of the model and algorithms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45758/1/11336_2005_Article_BF02295730.pd

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease