Establishment of a clinical network for children with amelogenesis imperfecta and dentinogenesis imperfecta in the UK: 4-year experience.

BACKGROUND: Amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are two groups of genetically inherited conditions resulting in abnormal enamel and dentin formation, respectively. Children and young people may be adversely affected by these conditions, with significant reduction in oral health related quality of life. Dental management of children with AI and DI is often complex, which is exacerbated by the absence of clear referral pathways and scarce evidence-based guidelines. METHOD: The need for increased knowledge and peer support led to the development of a group of UK paediatric dentists with a special clinical interest in the management of children with AI and DI. PURPOSE: The aims of this paper are to describe the establishment of an AI/DI Clinical Excellence Network (AI/DI CEN) in paediatric dentistry including outputs and future plans, and to share our collective learning to help support others anywhere in the world advance the care of people with AI or DI.

Best clinical practice guidance for treating deep carious lesions in primary teeth: an EAPD policy document.

PURPOSE: The European Academy of Paediatric Dentistry (EAPD) has developed this best clinical practice guidance to help clinicians manage deep carious lesions in primary teeth. METHODS: Three expert groups conducted systematic reviews of the relevant literature. The topics were: (1) conventional techniques (2) Minimal Intervention Dentistry (MID) and (3) materials. Workshops were held during the corresponding EAPD interim seminar in Oslo in April 2021. Several clinical based recommendations and statements were agreed upon, and gaps in our knowledge were identified. RESULTS: There is strong evidence that indirect pulp capping and pulpotomy techniques, and 38% Silver Diamine Fluoride are shown to be effective for the management of caries in the primary dentition. Due to the strict criteria, it is not possible to give clear recommendations on which materials are most appropriate for restoring primary teeth with deep carious lesions. Atraumatic Restorative Technique (ART) is not suitable for multi-surface caries, and Pre-formed Metal Crowns (PMCs) using the Hall technique reduce patient discomfort. GIC and RMGIC seem to be more favourable given the lower annual failure rate compared to HVGIC and MRGIC. Glass carbomer cannot be recommended due to inferior marginal adaptation and fractures. Compomers, hybrid composite resins and bulk-fill composite resins demonstrated similar values for annual failure rates. CONCLUSION: The management of deep carious lesions in primary teeth can be challenging and must consider the patient's compliance, operator skills, materials and costs. There is a clear need to increase the use of MID techniques in managing carious primary teeth as a mainstream rather than a compromise option.

Patient-reported outcome measures for children and adolescents having dental bleaching in the UK.

PURPOSE: Dental bleaching in paediatric patients can be used to address discolouration of teeth due to trauma, endodontic treatment, or enamel and dentine defects. Despite being a minimally invasive and successful treatment, the use of bleaching products in children and young people remains controversial. This evaluation was designed to provide insight into the child's perspective on dental bleaching and the influence that this treatment has upon their life. METHOD: A dental bleaching patient reported outcome measure (PROM) was developed and piloted in 2019. Data were collected from 3 UK units (January-March 2020). Children attending these units for bleaching reviews were invited to complete the PROM. RESULTS: Twenty seven PROM questionnaires were completed including 19 courses of external bleaching and 8 courses of internal/external bleaching. The average age was 14 years old (9-17 years). The common indications for bleaching were Amelogenesis Imperfecta, dental trauma and Molar Incisor Hypomineralisation. Patients reported improvements in their appearance (89%) and self-confidence (81%). Sensitivity was the most common side effect, reported in 63% of cases. CONCLUSION: This PROM supports the use of dental bleaching in children and young people when treating dental disease that causes discolouration. Bleaching not only improved the appearance of teeth, but also patients' self-confidence. Sensitivity is a common side effect and clinicians should discuss this common risk and its management with patients and their families.

Effectiveness of a novel, non-intrusive, continuous-use air decontamination technology to reduce microbial contamination in clinical settings: a multi-centric study.

BACKGROUND: Despite rigorous disinfection and fumigation, healthcare-associated infection (HAI) remains a significant concern in healthcare settings. We have developed a novel airborne-microbicidal technology 'ZeBox' which clears >99.999% of airborne microbial load under controlled laboratory conditions. AIM: To evaluate the clinical performance of ZeBox in reducing airborne and surface microbial load. METHODS: The study was conducted in single-bed and multi-bed intensive care units (ICUs) of two hospitals. Airborne and surface microbial loads were sampled pre and post deployment of ZeBox at pre-determined sites. Statistical significance of the reduction was determined using the Mann-Whitney U-test. FINDINGS: ZeBox brought statistically significant reduction of both airborne and surface bacterial and fungal load. In both hospital ICUs, airborne and surface bacterial load decreased by 90% and 75% on average respectively, providing a low bioburden zone of 10-15 feet diameter around the unit. The reduced microbial level was maintained during ZeBox's operation over several weeks. Most clinical bacterial isolates recovered from one of the hospitals were antibiotic resistant, highlighting ZeBox's ability to eliminate antimicrobial-resistant bacteria among others. CONCLUSION: ZeBox significantly reduces airborne and surface microbial burden in clinical settings. It thereby serves an unmet need for reducing the incidence of HAI.

Oral health-related quality of life in children with osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) results from mutations in the genes involved in the modification or biosynthesis of collagen. This study aimed to assess the oral health-related quality of life (OHRQoL) in children with OI. METHODOLOGY: Participants were recruited from a highly specialised OI centre for children. The Child Oral-Health Impact Profile-Short Form (COHIP-SF) was used, adding demographic and qualitative questions. Children aged 8-16 years participated between January and October 2019. Statistical analysis was carried out. A higher COHIP-SF score indicates better OHRQoL (maximum score, 76). RESULTS: One hundred and six (106) children participated (44 female, mean age 11.93 years). COHIP-SF median score was 59. Children reporting mild OI (n = 55) had higher median scores (62) compared to severe OI (n = 7) with median scores of 55 (P = 0.087). When comparing mixed (< 12 years, n = 46) and permanent dentition (≥ 12, n = 60), no significant difference in OHRQoL was seen (P = 0.977). There was no significant difference between severities for each COHIP-SF domain. Limited data on the presence of dentinogenesis imperfecta did not impact overall score (P = 0.109), but was significant in the oral-health domain (P = 0.033). QUALITATIVE: Common themes were the need for braces, discolouration, pain and function. CONCLUSION: This study confirmed that children with OI have dental concerns in areas including oral health, functional well-being and socio-emotional well-being. This was related to severity of OI.

The burden of dental care in Amelogenesis Imperfecta paediatric patients in the UK NHS: a retrospective, multi-centred analysis.

PURPOSE: The burden of dental care in Amelogenesis Imperfecta (AI) has not been well described. This condition results in weak, discoloured and often sensitive teeth. Specialist paediatric care is available for AI patients in the UK, but treatment protocols and care provided are inconsistent. The aim of this study was therefore to analyse the provision of treatment and burden of care for children and families with AI across four Paediatric Dentistry centres in the UK. METHODS: A retrospective evaluation of AI patient clinical records across four UK consultant-led Paediatric Dentistry centres was completed. Frequency and duration of care were recorded along with treatment and experience of inhalation sedation, local and general anaesthetic. RESULTS: In total, 138 records were available for analysis. The average patient age at first referral was 7.7 years (range 1-16 years) and families travelled an average 21.8 miles per appointment (range 0.2-286 miles). Patients attended on average 4.5 appointments per year for 5.8 years. In total, 65.2% had experience of local anaesthetic, 27.5% inhalation sedation and 31.9% general anaesthetic. Dental treatment including restorations and extractions were commonly required on multiple teeth per patient. CONCLUSION: AI carries a high burden of specialist dental care to patients and families. Specialist centres are required to provide longitudinal, comprehensive care.

Is it time to reconsider the use of vital teeth bleaching in children and adolescents in Europe?

PURPOSE: The aim of this study was to determine whether carbamide peroxide is effective in bleaching vital permanent teeth in children. METHODS: A literature search was conducted using all keywords relevant to the research subject. The outcome measures were identified as colour change, tooth sensitivity, oral irritation and patient satisfaction. The certainty of evidence for each outcome was assessed using the current GRADE guidelines. RESULTS: Of 115 potentially relevant articles, 112 were excluded, as they did not exclusively involve children, intervention involved additional treatment such as microabrasion or restorative work, or case studies. Patient satisfaction was not assessed in the three articles so no analysis could be made with regards to this outcome. The GRADE assessment showed that all of the three articles demonstrated very low certainty of evidence for the other assessed outcomes. The overall findings from the studies suggest that a 10% carbamide peroxide overnight tray system is effective at bleaching vital permanent teeth in children and associated tooth sensitivity and oral irritation are found to be in a similar range compared to those reported in adult studies. However, due to the very low certainty of the evidence, it is not possible to draw these conclusions. CONCLUSION: Better quality randomised controlled trials are needed to investigate the indication, short and long term effectiveness and side effects of carbamide teeth in vital permanent teeth in children.

Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report.

BACKGROUND: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. CASE PRESENTATION: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. CONCLUSION: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).

Developing a child patient satisfaction survey: a quality improvement project.

AIM: To develop a child-centred patient satisfaction questionnaire for use in an Outpatient Paediatric Dental Department. METHOD: Data from patient satisfaction interviews was used to develop a child satisfaction questionnaire, which was used in two different centres after piloting. RESULTS: The final questionnaire contained 7 questions and a comments section, using writing and facial images used to record children views. The questionnaire was distributed to 203 children; 95% were happy or okay with the waiting area, 69% were happy about seeing the dentist and 77% children were happy overall. CONCLUSION: Measures of satisfaction of children with regard to dental treatment were very different from those commonly used for adults. Further development and implementation of child satisfaction surveys should be considered.

Vital bleaching for children with dental anomalies: EAPD members' survey.

AIM: Understand EAPD members' practices of vital bleaching for children with dental anomalies. METHODS: An anonymous online survey sent via EAPD in January 2019, consisting of 13 questions with possible multiple answers and free text. RESULTS: 110 responses from 24 countries were obtained. The majority worked in hospitals/universities (n = 69, 63%) or private practices (n = 50, 46%) and were specialists (n = 62, 57%) or senior academics (n = 35, 32%). Most respondents (n = 74 68%) did not provide vital bleaching for children. 88 respondents (80%) belonged to EU: of these, 46 (52%) were not aware of bleaching regulations. For respondents who provided bleaching 26 (72%) undertook home bleaching, using 10% carbamide peroxide (n = 21, 58%), most commonly for 2 weeks (n = 14, 39%), following establishment of the permanent dentition (n = 21, 58%). Deciding factors included: extent (n = 27, 75%) and shade (n = 26, 72%) of discolouration and child being teased by peers (n = 23, 64%). Main reasons for not bleaching included: concerns with side effects (n = 41; 55%) and not agreeing with bleaching (n = 23, 31%). Dentists who did not bleach managed a range of conditions, most frequently molar-incisor hypomineralisation (n = 57; 77%). The majority provided composite restorations with removal of tooth structure (n = 50; 68%) with a number opting for no treatment (n = 27, 37%). CONCLUSION: This study shows wide variations in treatment of children's dental anomalies across Europe. Fears of adverse effects and personal beliefs seemed to be the main deterrents to bleaching in children. Clinicians who provided bleaching tended to opt for more conservative techniques and to take children's concerns into consideration.

Methods of space maintenance for premature loss of a primary molar: a review.

AIM: This critical appraisal attempts to answer the question: What is the best method of space maintenance (SM) following premature loss of a primary molar in children under 12 years old? METHODS: A search to identify studies relevant to the PICO was conducted. Single case reports and studies prior to 1986 were excluded. The principles of GRADE were followed to appraise the evidence. RESULTS: 20 studies were identified, which evaluated 2265 space maintainers (SMs). Two studies were graded high quality, four moderate, eight low, and six very low. All studies reported on longevity outcomes and most on adverse effects. CONCLUSIONS: There was no strong evidence favouring a particular SM, the following recommendations were made: (a) strong recommendations: In cases where rubber dam cannot be used clinicians should not use Glass Fibre Reinforced Composite Resin (GFRCR) SMs. (b) Weak recommendations: Crown and Loop SMs are recommended for loss of primary first molars; GFRCR SMs (placed under rubber dam) are recommended for loss of primary second molars. Bilateral SMs may have questionable efficacy and their use where there is loss of multiple molars in the same quadrant should be weighed against the risk of unwanted tooth movements, loss of a removable SM or no space maintenance at all.

Integrative network analysis identifies novel drivers of pathogenesis and progression in newly diagnosed multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells characterized by wide clinical and molecular heterogeneity. In this study we applied an integrative network biology approach to molecular and clinical data measured from 450 patients with newly diagnosed MM from the MMRF (Multiple Myeloma Research Foundation) CoMMpass study. A novel network model of myeloma (MMNet) was constructed, revealing complex molecular disease patterns and novel associations between clinical traits and genomic markers. Genomic alterations and groups of coexpressed genes correlate with disease stage, tumor clonality and early progression. We validated CDC42BPA and CLEC11A as novel regulators and candidate therapeutic targets of MMSET-related myeloma. We then used MMNet to discover novel genes associated with high-risk myeloma and identified a novel four-gene prognostic signature. We identified new patient classes defined by network features and enriched for clinically relevant genetic events, pathways and deregulated genes. Finally, we demonstrated the ability of deep sequencing techniques to detect relevant structural rearrangements, providing evidence that encourages wider use of such technologies in clinical practice. An integrative network analysis of CoMMpass data identified new insights into multiple myeloma disease biology and provided improved molecular features for diagnosing and stratifying patients, as well as additional molecular targets for therapeutic alternatives.

Treatment of HCV infection in liver transplant recipients with ledipasvir and sofosbuvir without ribavirin.

BACKGROUND: Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. AIM: To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. RESULTS: A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9 years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. CONCLUSION: Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

Self-referenced ultra-broadband transient terahertz spectroscopy using air-photonics.

Terahertz (THz) air-photonics employs nonlinear interactions of ultrashort laser pulses in air to generate and detect THz pulses. As air is virtually non-dispersive, the optical-THz phase matching condition is automatically met, thus permitting the generation and detection of ultra-broadband THz pulses covering the entire THz spectral range without any gaps. Air-photonics naturally offers unique opportunities for ultra-broadband transient THz spectroscopy, yet many critical challenges inherent to this technique must first be resolved. Here, we present explicit guidelines for ultra-broadband transient THz spectroscopy with air-photonics, including a novel method for self-referenced signal acquisition minimizing the phase error, and the numerically-accurate approach to the transient reflectance data analysis.

Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?

BACKGROUND: Recent studies have led to an expansion of potential factors capable of stimulating obesity. Increasing evidence indicates that environmental factors, including disturbance of circadian rhythms, also contribute to its etiology. OBJECTIVES: To determine the effects of altered circadian rhythms on adipogenesis and to better understand how circadian and adipogenic regulatory pathways are linked, zebrafish larvae were exposed to various light/dark cycles or hypercaloric feeding (HCF). METHODS: Clock and adipogenic gene expression was quantitative real time PCR. Adipogenesis was characterized using coherent anti-Stokes Raman scattering microscopy (CARS) and whole-mount lipid composition was analyzed by gas chromatography. The clock protein Rev-erbα and the adipogenesis-regulating protein Pparγ were localized by immunohistochemistry. RESULTS: Zebrafish larvae exposed to continuous light (LL) had a sevenfold higher prevalence of adipocytes compared with control fish under a 14 h light and 10 h dark cycle. It was also significantly higher compared with that in HCF larvae with control light/dark cycle, which showed a 5.5-fold increase compared with control animals. Although total fatty acid content was unaffected, adipocyte lipid composition was altered in LL zebrafish. In contrast, shifting the onset and duration of the light periods did not affect adipogenesis or total fatty acid content. Gene expression analysis revealed effects of LL and HCF on circadian cyclicity, with increased expression of the clock gene period2 and altered circadian rev-erbα expression in LL larvae. Immunostaining revealed for the first time that Rev-erbα and Pparγ colocalize in adipocytes, which together with the gene expression analysis suggests interplay between Rev-erbα and Ppar isoforms. CONCLUSIONS: The amount of light, but not shifted light/dark cycles, affected adipogenesis and lipid composition, possibly due to increased period2 expression, which, in turn, enhances Rev-erbα-regulated gene expression. As the pparßδ promoter includes three Rev-erbα binding sites, we hypothesize that pparßδ may be a direct target that ultimately activates Pparγ.

A systematic review of the public's knowledge and beliefs about antibiotic resistance.

OBJECTIVES: The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance. METHODS: We searched four databases to July 2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes. RESULTS: Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants [median 70% (IQR 50%-84%); n = 8 studies] had heard of antibiotic resistance, but most [median 88% (IQR 86%-89%); n = 2 studies] believed it referred to changes in the human body. Many believed excessive antibiotic use [median 70% (IQR 59%-77%); n = 11 studies] and not completing antibiotic courses [median 62% (IQR 47%-77%); n = 8 studies] caused resistance. Most participants nominated reducing antibiotic use [median 74% (IQR 72%-85%); n = 4 studies] and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians. CONCLUSIONS: The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.