A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. Objectives: To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. Methods: People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. Results: A total of 222 people were randomized. Baseline mean FEV1 was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; P = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; P = 0.019) and in those with an eosinophil count <300 cells/µl (RR, 0.50; 95% CI, 0.29-0.84; P = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months (P < 0.007). Conclusions: Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/µl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).

Part II: Blood Transfusion and Donor Exposure in the Surgical Management of Trigonocephaly Patients: A Protocol From Alder Hey Craniofacial Unit.

Trigonocephaly is a craniofacial malformation caused by premature fusion of the metopic suture. Surgical correction frequently results in the need for blood transfusion. Transfusion complications include transfusion-transmitted infections (TTIs), immune-mediated reactions, and volume overload. Donor exposure (DE) describes the number of blood products from unique donors with increasing DE equating to an increased risk of TTI. We evaluate data on 204 trigonocephaly patients covering 20 years of practice with respect to blood transfusions and DE. This represents the largest series from a single unit to date. A protocol based on our experiences has been devised that summarizes the key interventions we recommend to minimize blood transfusions and DE in craniofacial surgery. Patients operated on between 2000 and 2020 were included. DE and a range of values were calculated including estimated red cell loss (ERCL) and estimated red cell volume transfused (ERCVT). Groups were established by relevant interventions and compared using the Mann-Whitney U test. Mean DE fell from 1.46 at baseline to 0.85 ( P <0.05). Median allogenic transfusion volume fell from 350 mL at baseline to 250 mL ( P <0.05). Median ERCL fell from 15.05 mL/kg at baseline to 12.39 mL/kg and median ERCVT fell from 20.85 to 15.98 mL/kg. Changes in ERCL and ERCVT did not reach statistical significance. DE can be minimized with the introduction of key interventions such as a restrictive transfusion policy, preoperative iron, cell saver, tranexamic acid, and use of a matchstick burr for osteotomies.

The Paediatric Vault Score (PVS)-A Novel Scoring Tool for Prioritisation of Surgical Management of Craniosynostosis Patients.

Craniosynostosis is the premature fusion of the skull sutures, resulting in abnormal skull shape and volume. Timely management is a priority in avoiding raised intracranial pressure which can result in blindness and neurodevelopmental delay. Due to the COVID-19 pandemic, theater access was reduced. A risk stratification scoring system was thus devised to score patients attending surgery and aid in prioritization according to surgical need. The authors present the Paediatric Vault Score (PVS), which can also be customized to each unit's individual protocols. Ten patients on the waiting list were randomly selected and their clinical information was summarized in uniform anonymized reports. Six craniofacial consultants were selected as assessors and given 1 week to independently rank the patients from 1 to 10. Each scorer's ranking was verified against the PVS template and concordance was analyzed using the Kendall tau correlation coefficient (KT). Three cycles of the scoring process were carried out. Improvements were made to the scoring tool following cycle 1. Cycle 1 revealed 2 clinicians to be concordant with the PVS system and 4 to be discordant. Cycle 2 revealed all 6 clinicians to be concordant, with a mean KT score of 0.61. The final cycle revealed all 6 clinicians to be concordant, with a mean KT score of 0.70. Four scorers increased their concordance once the scoring sheet was introduced. Kendall's correlation of concordance calculated the interrater reliability to be 0.81. The PVS is the first known vault scoring system to aid in risk stratification and waiting list prioritization.

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. METHODS: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. INTERPRETATION: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. FUNDING: National Institute for Health Research Health Technology Assessment programme.

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.

BACKGROUND: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. METHODS: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5-12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). FINDINGS: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0-94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96-1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of -0·040 (95% central range -0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. INTERPRETATION: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Television advertisements for high-sugar foods and beverages: effect on children's snack food intake.

Energy-dense food advertising affects children's eating behaviour. However, the impact of high-sugar food advertising specifically on the intake of sweet foods is underexplored. This study sought to determine whether children would increase their intake of sugar and total energy following high-sugar food advertising (relative to toy advertising) and whether dental health, weight status and socio-economic status (SES) would moderate any effect. In a crossover, randomised controlled trial, 101 UK children (forty male) aged 8-10 years were exposed to high-sugar food/beverage and toy advertisements embedded within a cartoon. Their subsequent intake of snack foods and beverages varying in sugar content was measured. A dental examination was performed, and height and weight measurements were taken. Home postcode provided by parents was used to assign participants to SES quintiles. Children consumed a significantly greater amount of energy (203·3 (95 % CI 56·5, 350·2) kJ (48·6 (95 % CI 13·5, 83·7) kcal); P = 0·007) and sugar (6·0 (95 % CI 1·3, 10·7) g; P = 0·012) following food advertisements compared with after toy advertisements. This was driven by increased intake of the items with most sugar (chocolate and jelly sweets). Children of healthy weight and with dental caries had the greatest intake response to food advertising exposure, but there were no differences by SES. Acute experimental food advertising exposure increases food intake in children. Specifically, high-sugar food and beverage advertising promotes the consumption of high-sugar food items. The debate around the negative health effects of food advertising on children should be widened to include dental health as well as overall dietary health and obesity.

Clinical outcomes of single implant supported crowns versus 3-unit implant-supported fixed dental prostheses in Dubai Health Authority: a retrospective study.

BACKGROUND: This study assessed retrospectively the clinical outcomes of single implant-supported crowns and implant-supported fixed dental prostheses (FDPs). METHODS: This case series compared biological and technical complications in single implant-supported crowns and implant-supported bridges in a time framed sample of all patients who received dental implants between 2009 and 2016 in Dubai Health Authority. Only 3-unit implant-supported prostheses (FDPs) with one intervening pontic and an implant each end were included for comparison to single crown supported implants. Cantilevered implants, implant-supported dentures and cases involving bone grafts or sinus lifts were excluded. The primary outcome measure was marginal bone loss, measured on digital radiographs taken after prosthesis placement at baseline and one year after implant loading, whilst peri-implantitis and technical complications were secondary outcomes. Mixed regression models adjusted for clustering of implants within patients was used for patient and implant factor associations. RESULTS: A total of 454 patients (152 males; 302 females) had 1673 implants. The mean age of males (53.7 years, SD 14.6) was significantly greater than females (49.3 years, SD 12.9, p < 0.001). Mean mesial bone loss on the FDPs was significantly greater at 1 year (1.14 mm, SD 0.63) compared with the mesial surface of single implant-supported crowns (0.30 mm, SD 0.43, p < 0.001). Mean distal bone loss was also significantly greater at 1 year on the distal surfaces of implants supporting bridgework (1.29 mm, SD 0.71) compared with distal surfaces on single implant-supported crowns (0.36 mm, SD 0.54, p < 0.001). Mean marginal bone loss mesially and distally around implants placed in the lower anterior sextant was significantly greater compared to all other sites (p < 0.001). Bone loss by gender, patient's age and medical condition was not different between the 2 implant groups. Screw loosening was the main technical complication (11.5%) whilst peri-implantitis occurred rarely (0.5%). The 66 cement retained implants had significantly more complications compared to the 1607 screw retained implants (p < 0.001). CONCLUSIONS: Mean marginal bone loss around the supporting implants of FDPs (3-unit fixed bridgework) was greater than on single implant-supported crowns at one year after implant loading. Position in the mouth was associated with bone loss. Biological and technical complications occurred rarely.

Teaching orthodontic emergencies using the "flipped classroom" method of teaching-A mixed methods RCT.

INTRODUCTION: In the United Kingdom, the General Dental Council requires newly graduated dentists to be competent in managing orthodontic emergencies. Undergraduate students typically receive limited exposure to orthodontics, with teaching primarily delivered via conventional lectures. Flipped teaching involves knowledge being acquired in students' own time, with class time focussing on construction of meaning. METHODS: A total of 61 undergraduate dental students were randomised into either a flipped or a conventional group. The conventional group (n = 30) attended a lecture describing the management of six common emergencies. The flipped group (n = 31) were given access to six videos via a virtual learning environment and later completed practical tasks related to the material. Both groups completed a single best answer assessment. Perceptions of flipped classroom teaching were explored via focus groups. RESULTS: For questions on orthodontic emergencies, the conventional group had a mean examination result of 70.5% (SD 8.0%) compared with the flipped group of 72.8% (SD 12.9%). There was no significant difference between the groups (P = .532). For regular orthodontic questions, the conventional group had a mean examination result of 64.8% (SD: 19.9%) compared with 78.3% (SD: 21.7%). There was no significant difference between the groups (P = .083). Thematic analysis identified the following themes: ways in which videos encourages more effective learning, improved engagement, awareness of learning needs and proposed teaching/curriculum changes. The overarching theoretical perspective was facilitating an experiential learning cycle using flipped classroom teaching. CONCLUSIONS: In the context of this investigation, the flipped classroom method of teaching resulted in comparable examination performance and improved levels of satisfaction.

Development of a patient reported outcome measures for measuring the impact of visual impairment following stroke.

BACKGROUND: Among the available patient-reported outcome measures (PROMs) there is an absence of a PROM with a specific focus on the impact of the wide variety of visual impairments following stroke. Our aim was to develop a patient reported quality of life outcome measure for stroke survivors with visual impairment. METHODS: Potential items were sourced from a combination of existing PROMs from a systematic review and qualitative in-depth interviews, duplicates were removed and items shortlisted. The initial pilot instrument was created following a ranking exercise of these potential items and consultation with stroke survivors. Version 1 was piloted with 37 stroke survivors at acute and chronic stages. Version 2 was piloted with 243 stroke survivors with visual impairment at acute and chronic stages. This data was analysed using the Rasch measurement model. Simultaneously, items from Version 2 underwent a Delphi process with stroke survivors and stroke clinicians, to assess the importance of each item. Final consensus decisions on item removal were made using the combined analysis from the Rasch measurement model and Delphi process in a nominal group meeting. RESULTS: Due to the wide range of rank given to the majority of categories/items, only two items were discarded. Version 1 comprised of 102 items with 5 response categories relating to amount of difficulty. The pilot of Version 1 allowed item reduction based on analysis of floor/ceiling effects and not applicable responses. Version 2 comprised of 62 items. Within the nominal group meeting, the expert panel created a set of rules which aided them with decision making in addition to the Rasch and Delphi analysis data. This resulted in the removal of 43 items and the combination of seven items to create three new items. The expert panel also recommended the rewording of three items. CONCLUSION: The Brain Injury associated Visual Impairment Impact Questionnaire (BIVI-IQ-15), a 15-item instrument with 4 response categories has been developed for capturing vision-related quality of life of stroke survivors with any of the predominant types of visual impairment, in the presence of other impairments and for both inpatients and outpatients.

Comparison of statural height growth velocity at different cervical vertebral maturation stages.

INTRODUCTION: Knowledge of a patient's stage of growth and development plays a vital role in diagnosis, treatment planning, results, and stability of the outcome. Cervical vertebral maturation (CVM) predicts the stage of growth and development, but its validity has only been investigated restrospectively, using historic samples. Our objective was to assess prospectively whether a correlation exists between CVM stage and statural height growth velocity. METHODS: Participants were aged between 8 and 18 years and of both sexes. Standing height was measured every 6 weeks with participants barefoot and in natural head position. CVM stage was assessed from lateral cephalograms taken at the start of treatment. Intraobserver and interobserver reliability of CVM staging and statural height measurements were assessed using the Cohen weighted kappa, percentage of agreement, intraclass correlation coefficient, and Bland-Altman plots, respectively. Analysis of variance was used to test for statistically significant differences between growth velocities at the CVM stages. RESULTS: We analyzed 108 participants. The peak in statural height growth velocity occurred at CVM stage 3 (P = 0.001). There was a statistically significant difference in the mean annualized growth velocity between all CVM stages except stages 2 and 4. Girls had their peak pubertal growth spurt an average of 1.2 years earlier than did boys. CONCLUSIONS: This study suggests that there is a significant relationship between CVM stage and statural height velocity.

The Scottish Orthodontic Peer Review project: the outcome of treatment and standard of record keeping by orthodontic specialist practitioners in Scotland.

OBJECTIVES: Assess occlusal outcomes of treatment and clinical record keeping in specialist practice in Scotland. DESIGN: A retrospective cohort study. SETTING: Specialist practices in Scotland. PARTICIPANTS: Specialist orthodontists in Scotland. METHODS: Every specialist practitioner in Scotland (51) was invited to take part in the peer review project with 38 (76%) enrolled. Scotland was split into four geographical areas, and each practitioner matched with a colleague from the same area. Practitioners took one day to visit their colleague and score 30 consecutively treated NHS cases using the Peer Assessment Rating (PAR) index. They also assessed the quality of the records taken. Practitioners then swapped roles and assessed their partner's occlusal outcomes and records. RESULTS: The mean pretreatment PAR score was 28.6 (SD 3.5). Mean posttreatment PAR score was 3.5 (SD 1.2). Mean reduction in PAR score was 25.1 (SD 3.8). Mean percentage PAR score reduction was 87.7% (SD 3.7%). Overall record keeping scores were written records 100%, study models 99.5%, Orthopantomogram radiograph 99.2%, photographs 86.3%, medical history 75% and consent 40.8%. CONCLUSIONS: Occlusal outcomes achieved by specialist practitioners in Scotland were of a high standard. They maintained a good standard of clinical record collection in most areas examined.

Categorisation of tibial artery disease on computer tomography angiography according to the TASC II classification.

Purpose Computer tomography angiography is used to assess peripheral arterial disease. Its preference over other imaging modalities is based upon its rapid acquisition and high spatial resolution, along with ease of access. TASC II have recently updated their vascular lesion classification to include infrapopliteal lesions, and our aim is to assess the reproducibility of TASC II on infrapopliteal disease when using computer tomography angiography. Methods A retrospective analysis of a series of consecutive computer tomography angiographies was performed by seven assessors (three consultant radiologists, two consultant vascular surgeons and two vascular specialty trainees). Each assessor was asked to classify the target vessel based on the TASC II classification. Statistical analysis was performed using Cohen's weighted kappa. Results Seven assessors analysed 48 target vessels in 25 patients (20 men), with a mean age of 72.9 years. Twenty posterior tibial, 27 anterior tibial and one peroneal artery were analysed. Poor agreement was demonstrated between the two vascular consultants, with a kappa of 0.094. Weak agreement was demonstrated among the radiologists, with a kappa of 0.547. The total group of assessors had a kappa of 0.176. Conclusion This study showed poor agreement between assessors when applying the TASC II classification to infrapopliteal lesions on computer tomography angiography. TASC II should not be used to classify lesions, for clinical or research purposes, with this image modality.

An assessment of the impacts of child oral health in Indonesia and associations with self-esteem, school performance and perceived employability.

BACKGROUND: Previous surveys have indicated that a majority of Indonesian children have poor oral health. However, little detailed information is available on underlying causation and none that examine impacts of oral health on child self-esteem, school performance and perceived employability. The aim of this study was to determine levels of child oral health in primary school children in Indonesia, the prevalence of key causal factors; and, to determine relationships between oral health, self-esteem and school academic performance. METHODS: Cross-sectional epidemiological study in a sample (n = 984) of children aged 6-7 and 10-11 years old attending three public schools in Indonesia. A dental visual impact study was conducted, in which teachers reported their perceptions of the impact of child oral health on school academic performance. Oral health behaviors, self-esteem, and school performance were assessed. The children were clinically examined to measure dental caries and oral cleanliness. RESULTS: Teachers believe that children with visually poor oral health and impaired smiles are more likely to perform poorly at school, be socially excluded and have lower job prospects than their peers with visually good oral health and healthy smiles. The percentages of children with decayed teeth were 94 and 90% in the 6-7- and 10-11-year age groups, respectively. Families reported high levels of child consumption of sugar-containing foods and drinks; many had irregular use of fluoride toothpaste. Children with substantial plaque on their teeth achieved significantly lower levels of school performance than their peers with clean teeth. Significant associations were found between school performance and self-esteem for these children. CONCLUSIONS: The study findings highlight the need for preventive care programs to improve the oral health of children in Indonesia and prospective determination of associations between child oral health; self-esteem and school academic performance.

A randomised controlled trial to investigate the remineralising potential of Tooth Mousse™ in orthodontic patients.

OBJECTIVE: To investigate the remineralisation of enamel subsurface lesions treated with fluoride toothpaste (1450 ppm) or a combination of fluoride toothpaste in addition to Tooth Mousse™. DESIGN: An in situ, cross-over, randomised controlled trial. SETTING: Orthodontic department at Liverpool University Dental Hospital, UK. PARTICIPANTS: Twelve patients receiving fixed orthodontic treatment. METHODS: Demineralised subsurface enamel lesions were placed in a carrier and attached onto a fixed orthodontic appliance. Interventions were either standard fluoride toothpaste or CPP-ACP paste (Tooth Mousse™) in addition to the fluoride toothpaste. Participants received both interventions in a randomised order. Transverse microradiography analysis was used to compare lesion mineral content profiles. RESULTS: Mineral loss was reduced by 15.4 and 24.6% between the fluoride and CPP-ACP groups, respectively (p = 0.023). Lesion depth was reduced by 1.6 and 11.1% between the fluoride and CPP-ACP groups, respectively (p = 0.037). Lesion width was reduced by 4.5 and 15.3% between the fluoride and CPP-ACP groups, respectively (p = 0.015). CONCLUSIONS: Remineralisation occurred regardless of treatment group allocation. However, the addition of Tooth Mousse™ resulted in a significantly increased remineralisation effect, compared to fluoride alone. Tooth Mousse™ may be beneficial for patients undergoing orthodontic treatment who are at high risk of demineralisation. TRIAL REGISTRATION: Registered on Current Control Trials http://www.controlled-trials.com/ISRCTN04899524.

A randomized trial of genotype-guided dosing of warfarin.

BACKGROUND: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. METHODS: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. RESULTS: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). CONCLUSIONS: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).

Reliability of cervical vertebral maturation staging.

INTRODUCTION: Growth and its prediction are important for the success of many orthodontic treatments. The aim of this study was to determine the reliability of the cervical vertebral maturation (CVM) method for the assessment of mandibular growth. METHODS: A group of 20 orthodontic clinicians, inexperienced in CVM staging, was trained to use the improved version of the CVM method for the assessment of mandibular growth with a teaching program. They independently assessed 72 consecutive lateral cephalograms, taken at Liverpool University Dental Hospital, on 2 occasions. The cephalograms were presented in 2 different random orders and interspersed with 11 additional images for standardization. The intraobserver and interobserver agreement values were evaluated using the weighted kappa statistic. RESULTS: The intraobserver and interobserver agreement values were substantial (weighted kappa, 0.6-0.8). The overall intraobserver agreement was 0.70 (SE, 0.01), with average agreement of 89%. The interobserver agreement values were 0.68 (SE, 0.03) for phase 1 and 0.66 (SE, 0.03) for phase 2, with average interobserver agreement of 88%. CONCLUSIONS: The intraobserver and interobserver agreement values of classifying the vertebral stages with the CVM method were substantial. These findings demonstrate that this method of CVM classification is reproducible and reliable.

Assessing the association between oral hygiene and preterm birth by quantitative light-induced fluorescence.

The aim of this study was to investigate the purported link between oral hygiene and preterm birth by using image analysis tools to quantify dental plaque biofilm. Volunteers (n = 91) attending an antenatal clinic were identified as those considered to be "at high risk" of preterm delivery (i.e., a previous history of idiopathic preterm delivery, case group) or those who were not considered to be at risk (control group). The women had images of their anterior teeth captured using quantitative light-induced fluorescence (QLF). These images were analysed to calculate the amount of red fluorescent plaque (ΔR%) and percentage of plaque coverage. QLF showed little difference in ΔR% between the two groups, 65.00% case versus 68.70% control, whereas there was 19.29% difference with regard to the mean plaque coverage, 25.50% case versus 20.58% control. A logistic regression model showed a significant association between plaque coverage and case/control status (P = 0.031), controlling for other potential predictor variables, namely, smoking status, maternal age, and body mass index (BMI).

COVID-19 risk mitigation in reopening mass cultural events: population-based observational study for the UK Events Research Programme in Liverpool City Region.

OBJECTIVES: To understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risks, perceived risks and the feasibility of risk mitigations from experimental mass cultural events before coronavirus disease 2019 (COVID-19) restrictions were lifted. DESIGN: Prospective, population-wide observational study. SETTING: Four events (two nightclubs, an outdoor music festival and a business conference) open to Liverpool City Region UK residents, requiring a negative lateral flow test (LFT) within the 36 h before the event, but not requiring social distancing or face-coverings. PARTICIPANTS: A total of 12,256 individuals attending one or more events between 28 April and 2 May 2021. MAIN OUTCOME MEASURES: SARS-CoV-2 infections detected using audience self-swabbed (5-7 days post-event) polymerase chain reaction (PCR) tests, with viral genomic analysis of cases, plus linked National Health Service COVID-19 testing data. Audience experiences were gathered via questionnaires, focus groups and social media. Indoor CO2 concentrations were monitored. RESULTS: A total of 12 PCR-positive cases (likely 4 index, 8 primary or secondary), 10 from the nightclubs. Two further cases had positive LFTs but no PCR. A total of 11,896 (97.1%) participants with scanned tickets were matched to a negative pre-event LFT: 4972 (40.6%) returned a PCR within a week. CO2 concentrations showed areas for improving ventilation at the nightclubs. Population infection rates were low, yet with a concurrent outbreak of >50 linked cases around a local swimming pool without equivalent risk mitigations. Audience anxiety was low and enjoyment high. CONCLUSIONS: We observed minor SARS-CoV-2 transmission and low perceived risks around events when prevalence was low and risk mitigations prominent. Partnership between audiences, event organisers and public health services, supported by information systems with real-time linked data, can improve health security for mass cultural events.

Primary school-based behavioural interventions for preventing caries.

BACKGROUND: Dental caries is one of the most common global childhood diseases and is, for the most part, entirely preventable. Good oral health is dependent on the establishment of the key behaviours of toothbrushing with fluoride toothpaste and controlling sugar snacking. Primary schools provide a potential setting in which these behavioural interventions can support children to develop independent and habitual healthy behaviours. OBJECTIVES: To assess the clinical effects of school-based interventions aimed at changing behaviour related to toothbrushing habits and the frequency of consumption of cariogenic food and drink in children (4 to 12 year olds) for caries prevention. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 18 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), MEDLINE via OVID (1948 to 18 October 2012), EMBASE via OVID (1980 to 18 October 2012), CINAHL via EBSCO (1981 to 18 October 2012) and PsycINFO via OVID (1950 to 18 October 2012). Ongoing trials were searched for using Current Controlled Trials (to 18 October 2012) and ClinicalTrials.gov (to 18 October 2012). Conference proceedings were searched for using ZETOC (1993 to 18 October 2012) and Web of Science (1990 to 18 October 2012). We searched for thesis abstracts using the Proquest Dissertations and Theses database (1950 to 18 October 2012). There were no restrictions regarding language or date of publication. Non-English language papers were included and translated in full by native speakers. SELECTION CRITERIA: Randomised controlled trials of behavioural interventions in primary schools (children aged 4 to 12 years at baseline) were selected. Included studies had to include behavioural interventions addressing both toothbrushing and consumption of cariogenic foods or drinks and have a primary school as a focus for delivery of the intervention. DATA COLLECTION AND ANALYSIS: Two pairs of review authors independently extracted data related to methods, participants, intervention design including behaviour change techniques (BCTs) utilised, outcome measures and risk of bias. Relevant statistical information was assessed by a statistician subsequently. All included studies contact authors were emailed for copies of intervention materials. Additionally, three attempts were made to contact study authors to clarify missing information. MAIN RESULTS: We included four studies involving 2302 children. One study was at unclear risk of bias and three were at high risk of bias. Included studies reported heterogeneity in both the intervention design and outcome measures used; this made statistical comparison difficult. Additionally this review is limited by poor reporting of intervention procedure and design. Several BCTs were identified in the trials: these included information around the consequences of twice daily brushing and controlling sugar snacking; information on consequences of adverse behaviour and instruction and demonstration regarding skill development of relevant oral health behaviours.Only one included study reported the primary outcome of development of caries. This small study at unclear risk of bias showed a prevented fraction of 0.65 (95% confidence interval (CI) 0.12 to 1.18) in the intervention group. However, as this is based on a single study, this finding should be interpreted with caution.Although no meta-analysis was performed with respect to plaque outcomes (due to differences in plaque reporting between studies), the three studies which reported plaque outcomes all found a statistically significant reduction in plaque in the intervention groups with respect to plaque outcomes. Two of these trials involved an 'active' home component where parents were given tasks relating to the school oral health programme (games and homework) to complete with their children. Secondary outcome measures from one study reported that the intervention had a positive impact upon children's oral health knowledge. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence for the efficacy of primary school-based behavioural interventions for reducing caries. There is limited evidence for the effectiveness of these interventions on plaque outcomes and on children's oral health knowledge acquisition. None of the included interventions were reported as being based on or derived from behavioural theory. There is a need for further high quality research to utilise theory in the design and evaluation of interventions for changing oral health related behaviours in children and their parents.