Participation of paediatric patients in primary dental care before and after a dental general anaesthetic.

PURPOSE: The aim of this retrospective study is to determine children's attendance and experience of preventative interventions and operative treatment (restorations and extractions) with their primary care dentist (PCD) in the 12 months before and after their caries management under dental general anaesthetic (DGA). METHODS: A record of all children who had an elective DGA in 2016 across two hospital sites was retrospectively obtained (n = 1308). A representative sample of 300 was randomly selected encompassing 114 dental practices. An online questionnaire to the children's PCDs collated quantitative and qualitative data regarding participation in the pre- and post-DGA period. RESULTS: Data was collated and analysed for 80 children (mean age: 6 years 10 months [SD = 2.49; range: 2 years 1 month - 14 years 3 months]; equal sex distribution) with 43 responding PCDs. Attendance for examination declined significantly from 85% (n = 68) pre-DGA to 57.5% (n = 46) post-DGA (p ≤ 0.001). Attendance at emergency appointments pre-DGA was high (33.75% [n = 27]); a significant reduction post-DGA was recorded (p ≤ 0.001). Over one third of children (37.5% [n = 30]) did not receive any form of preventative intervention over 24 months. A non-significant reduction in the provision of operative treatment was observed post-DGA (p = 0.06 [fill, primary]; p = 0.78 [fill, permanent]; p = 0.66 [ext, primary]). No statistical difference between age and treatment experience was found. Qualitative analysis revealed challenges in providing care included behavioural difficulties and poor attendance. CONCLUSION: Improvements are required in strategies employed to support high caries risk children pre- and post-DGA to facilitate a higher incidence of attendance and preventative intervention with PCDs.

Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

PURPOSE: Thirty-day mortality of patients with hip fracture is well researched and predictive; validated scoring tools have been developed (Nottingham Hip Fracture Score, NHFS). COVID-19 has significantly greater mortality in the elderly and comorbid patients which includes hip fracture patients. Non-operative treatment is not appropriate due to significantly higher mortality, and therefore, these patients are often exposed to COVID-19 in the peri-operative period. What is unclear is the effect of concomitant COVID-19 infection in these patients. METHODS: A multicentre prospective study across ten sites in the United Kingdom (responsible for 7% of hip fracture patients per annum in the UK). Demographic and background information were collected by independent chart review. Data on surgical factors included American Society of Anesthesiologists (ASA) score, time to theatre, Nottingham Hip fracture score (NHFS) and classification of fracture were also collected between 1st March 2020 and 30th April 2020 with a matched cohort from the same period in 2019. RESULTS: Actual and expected 30-day mortality was found to be significantly higher than expected for 2020 COVID-19 positive patients (RR 3.00 95% CI 1.57-5.75, p < 0.001), with 30 observed deaths compared against the 10 expected from NHFS risk stratification. CONCLUSION: COVID-19 infection appears to be an independent risk factor for increased mortality in hip fracture patients. Whilst non-operative management of these fractures is not suggested due to the documented increased risks and mortality, this study provides evidence to the emerging literature of the severity of COVID-19 infection in surgical patients and the potential impact of COVID-19 on elective surgical patients in the peri-operative period.

Correction to: Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

The published online version contains mistake, as the Fig. 1 legend should read "Kaplan-Meier survival curve for 30-day survival for 2020 cohort COVID-19 positive vs COVID-19 negative" whilst the Fig. 2 legend should read "Kaplan-Meier survival curve for 30-day survival 2020 COVID-19 negative group vs 2019 cohort".

Displaced intracapsular neck of femur fractures: Outcome of 810 hydroxyapetite coated (HAC) uncemented hemiarthroplasties.

A Cochrane review influenced new NICE guidelines, which recommended surgeons: Offer cemented implants to patients undergoing surgery with arthroplasty. However our trust routinely uses HAC uncemented stem (Taperloc®, Biomet) hemiarthroplasties. A review of a consecutive series of uncemented HAC stem hemiarthroplasties including measures such as intro-operative complications, mortality and revision surgery. Prospectively collected data between January 2008 and June 2014 was used, with medical record and radiographic reviews performed. 810 consecutive Taperloc uncemented hemiarthroplasty with monopolar heads were performed in 763 patients, with a minimum 12 month follow-up (12-90) follow-up. Mean age 83yrs; 71% female. Meantime to operation was 28.5h. 30day mortality: 4.4% (33/763). One year mortality was 11.2% (89/763). 2.5% (20/810) were admitted on a separate admission with the periprosthetic fracture. 0.6% (5/810) were revised to total hip replacement for subsidence and associated pain. Only 1% (8/810) had intraoperative calcar fractures, all of which were treated with intraoperative cabling with no evidence of clinically relevant subsidence or medium term complications requiring revision surgery within a year. To the author's knowledge this is largest outcome series for modern design uncemented hemiarthroplasty. Our study shows comparable data to cemented hemiarthroplasty but no deaths in the first 2days post-op. Our series also demonstrates a well below average mortality figures which are clearly multifactorial but believe uncemented prosthesis play a role. We believe that uncemented proven stem design hemiarthroplasty remains a safe and good surgical option for displaced intracapsular fractures.

Ilizarov management of Schatzker IV to VI fractures of the tibial plateau: 105 fractures at a mean follow-up of 7.8 years.

This study aimed to determine the long-term functional, clinical and radiological outcomes in patients with Schatzker IV to VI fractures of the tibial plateau treated with an Ilizarov frame. Clinical, functional and radiological assessment was carried out at a minimum of one year post-operatively. A cohort of 105 patients (62 men, 43 women) with a mean age of 49 years (15 to 87) and a mean follow-up of 7.8 years (1 to 19) were reviewed. There were 18 type IV, 10 type V and 77 type VI fractures. All fractures united with a mean time to union of 20.1 weeks (10.6 to 42.3). No patient developed a deep infection. The median range of movement (ROM) of the knee was 110(°) and the median Iowa score was 85. Our study demonstrates good long-term functional outcome with no deep infection; spanning the knee had no detrimental effect on the ROM or functional outcome. High-energy fractures of the tibial plateau may be treated effectively with a fine wire Ilizarov fixator.

Practical considerations for conducting dental clinical trials in primary care.

There is increasing importance placed on conducting clinical trials in dentistry to provide a robust evidence base for the treatment provided, and models of care delivered. However, providing the evidence upon which to base such decisions is not straightforward, as the conduct of these trials is complex. Currently, only limited information is available about the strategies to deliver successful clinical trials in primary care settings, and even less available on dental clinical trials. Considerable knowledge and experience is lost once a trial is completed as details about effective management of a trial are generally not reported or disseminated to trial managers and researchers. This leads to loss of vital knowledge that could assist with the effective delivery of new trials. The aim of this study is to examine the conduct and delivery of five dental clinical trials across both Australia and the UK and identify the various factors that impacted upon their implementation. Findings suggest that early stakeholder engagement, and well-designed and managed trials, lead to improved outcomes for researchers, clinic staff and patients, and increases the potential for future dissemination and translation of information into practice.

Participant recruitment to FiCTION, a primary dental care trial - survey of facilitators and barriers.

OBJECTIVE: To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). SUBJECTS (MATERIALS) AND METHODS: An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. RESULTS: Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. CONCLUSIONS: These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team.

Extracts of irradiated mature human tooth crowns contain MMP-20 protein and activity.

OBJECTIVES: We recently demonstrated a significant correlation between enamel delamination and tooth-level radiation dose in oral cancer patients. Since radiation can induce the synthesis and activation of matrix metalloproteinases, we hypothesized that irradiated teeth may contain active matrix metalloproteinases. MATERIALS AND METHODS: Extracted teeth from oral cancer patients treated with radiotherapy and from healthy subjects were compared. Extracted mature third molars from healthy subjects were irradiated in vitro and/or incubated for 0-6 months at 37°C. All teeth were then pulverized, extracted, and extracts subjected to proteomic and enzymatic analyses. RESULTS: Screening of irradiated crown extracts using mass spectrometry identified MMP-20 (enamelysin) which is expressed developmentally in dentine and enamel but believed to be removed prior to tooth eruption. MMP-20 was composed of catalytically active forms at Mr=43, 41, 24 and 22kDa and was immunolocalized predominantly to the morphological dentine enamel junction. The proportion of different sized MMP-20 forms changed with incubation and irradiation. While the pattern was not altered directly by irradiation of healthy teeth with 70Gy, subsequent incubation at 37°C for 3-6 months with or without prior irradiation caused the proportion of Mr=24-22kDa MMP-20 bands to increase dramatically. Extracts of teeth from oral cancer patients who received >70Gy radiation also contained relatively more 24 and 22kDa MMP-20 than those of healthy age-related teeth. CONCLUSION: MMP-20 is a radiation-resistant component of mature tooth crowns enriched in the dentine-enamel. We speculate that MMP-20 catalyzed degradation of organic matrix at this site could lead to enamel delamination associated with oral cancer radiotherapy.

Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer

PURPOSE: Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. METHODS: The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. RESULTS: Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001). CONCLUSIONS: TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted (AU)

Sectioning of a double tooth aided by cone-beam computed tomography.

BACKGROUND: Double teeth present challenges for their clinical management. Recent advances in imaging, particularly cone-beam computed tomography (CBCT), have aided clinicians in accurate diagnosis and management. Data from CBCT imaging can be used for three-dimensional reconstruction to further aid pre-surgical planning. CASE REPORT: A 14-year-old Caucasian male presented with an aesthetically unacceptable double tooth in the 22 region. Clinical and radiographic examination and assessment included CBCT imaging and three-dimensional reconstruction. TREATMENT: Based on this information, together with a comprehensive assessment of the patient's motivation, a treatment plan consisting of extra-alveolar sectioning, re-implantation, endodontic therapy and composite resin restoration was carried out. FOLLOW-UP: The patient failed to return for follow-up at 6 months post-treatment. However, he did return at 12 months, where clinical and radiographic examination was undertaken. At this point the tooth was clinically sound and bony infill was seen radiographically. CONCLUSION: The information gained from the pre-surgical imaging with CBCT was useful in planning treatment in this case. However, this had to be combined with a careful assessment of the patient's motivation to ensure that the course of treatment embarked upon was likely to be successful whilst addressing the patient's concerns.

Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer.

PURPOSE: Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. METHODS: The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. RESULTS: Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001). CONCLUSIONS: TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

A pilot improvement project in hospital-based oral healthcare: improving caries risk assessment documentation.

OBJECTIVE: To evaluate the impact of a continuous improvement project to improve completion of a caries risk assessment (CRA) and to assess its impact on delivery of dental caries prevention. DESIGN: Single centre clinical improvement project. SETTING: A paediatric dental department within a UK dental hospital over the course of 2008-2009.Subjects (materials) and methods Continuous monitoring of documentation of a CRA was instigated and results fed back to clinicians. Tools were developed to structure the process of CRA. After six months of intervention, a comparison of preventive care to a pre-intervention sample was undertaken. MAIN OUTCOME MEASURES: The main outcome measure was completion of a CRA. Comparison was also made with pre-intervention data on levels of preventive care received. RESULTS: Over the 12 month project the mean rate of CRA completion improved from 30% over the first 6 months to 73% in the second 6 months. Compared to the pre-intervention sample, all items of the caries prevention package had improved, with delivery of toothpaste strength advice (16% vs 60%, p = 0.001) and diet advice (32% vs 70%, p = 0.004) improving significantly. CONCLUSION: By targeting and improving CRA completion the quality of preventive care delivered has also significantly improved.

Sigmoid sinus thrombosis presenting with posterior alexia in a patient with Behçet's disease and polycythaemia: a case report.

INTRODUCTION: A 59-year-old Caucasian woman presented with an acute onset of alexia, noticed whilst driving. She described how while she could read car number plates, she had lost the ability to read and understand words on roadside advertisements and car window stickers. CASE PRESENTATION: Neurological examination was unremarkable apart from the inability to read full words or sentences. Imaging of the brain, initially computed tomography, followed by magnetic resonance venography, confirmed a diagnosis of sigmoid sinus thrombosis with associated venous infarction. The patient's past medical history revealed that she had suffered an ischemic stroke and following investigation for this, had undergone a nephrectomy for renal cell carcinoma. This was complicated by postoperative deep venous thrombosis. She had a persistent polycythaemia that was managed with venesection, and recently she had been diagnosed with Behçet's disease. Prior to this presentation, she had recently stopped her prophylactic antiplatelet medication as she was due to undergo a total knee replacement for osteoarthritis. She was managed with weight-adjusted, low molecular weight heparin followed by oral anticoagulation, and made a good recovery from her symptoms. CONCLUSION: This case illustrates a classical neurological syndrome, highlights the importance of cerebral venous and sinus thrombosis as a cause of stroke, and the importance of remaining vigilant to a person's changing risk of venous thrombosis with evolving comorbidity.

Influence of a GT repeat element on shear stress responsiveness of the VWF gene promoter.

BACKGROUND: Plasma von Willebrand factor (VWF) is mainly derived from endothelial cells, cells that express a large repertoire of genes that are transcriptionally regulated by fluid shear stress. Endothelial VWF expression is not uniform throughout the vasculature, and levels are increased at regions associated with disturbed blood flow and steep gradients of shear stress. It is, however, unknown whether shear stress influences the regulation of VWF gene expression. OBJECTIVES: Our objective was to evaluate the effect of shear stress on endogenous endothelial VWF mRNA expression and VWF promoter (-2722 to -1224) activity and to determine whether genetic elements modulate this flow-induced expression. METHODS: A parallel plate flow chamber was used to expose endothelial cells to a shear level of 15 dynes cm(-2) for 24 or 6 h. VWF mRNA expression was analyzed. Various VWF promoter constructs that each contain either SNP haplotypes 1 or 2 and either a 17-GT or a 23-GT repeat element were transfected into endothelial cells, and flow-induced promoter activation was assessed. RESULTS: When endothelial cells were exposed to shear stress, endogenous VWF mRNA expression increased 1.84-fold and average VWF promoter activity was enhanced 3.4-fold. Single nucleotide polymorphisms at -2708 and -2525, and the shear stress-response element at -1585, are not responsible for the shear stress-induced increase. Rather a GT repeat element at -2124 mediates the increase in activity, and the length of this polymorphic repeat element influences the magnitude of induction. CONCLUSIONS: Shear stress enhances VWF promoter activity and a polymorphic GT repeat element mediates the stress-induced transactivation.

A single nucleotide polymorphism at nucleotide -1793 in the von Willebrand factor (VWF) regulatory region is associated with plasma VWF:Ag levels.

von Willebrand Factor (VWF) is a large multimeric glycoprotein involved in the transport and protection of factor VIII and in mediating platelet-subendothelium and platelet-platelet interactions. We have documented the presence of a single nucleotide polymorphism (SNP) at nucleotide (nt) -1793 (G 0.36 or C 0.64) in the VWF 5'-flanking sequence. This polymorphism is in strong linkage disequilibrium with the previously reported SNPs at nts -1234, -1185 and -1051 and, like this other group of polymorphisms, shows a significant association with plasma VWF levels. This association is more marked in subjects who are more than 40 years of age. Further, circumstantial evidence to support a role for the -1793 sequence in regulating VWF expression comes from our demonstration of differential binding of endothelial cell nuclear proteins, including the transcription factor NFkappaB, by this sequence. In summary, the association of the -1793 SNP with plasma VWF levels provides additional evidence for the role of the VWF regulatory region between nts -1793 and -1051 in controlling VWF expression.

Simultaneous presentation of both true and false aneurysm in the infrarenal aorta.

Interventional radiology has resulted in a reduced need for bypass procedures for aorto-occlusive disease. However, there are still indications for surgery of this type, which carries with it a small but significant morbidity and mortality. False aneurysms are well described following such procedures but with the development of inert, strong and non-absorbable materials they are becoming less common. This paper describes the acute presentation of a false aneurysm of the aorta following an aorto-iliac bypass where true aneurysmal change had taken place in the area of the anastomosis.

Variation at the von Willebrand factor (vWF) gene locus is associated with plasma vWF:Ag levels: identification of three novel single nucleotide polymorphisms in the vWF gene promoter.

Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5'-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40. 6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P =. 008; Kruskal-Wallis test, P =.006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P =.003; Kruskal-Wallis test, P =.001), but was not maintained for subjects .4; Kruskal-Wallis test, P >.4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFkappaB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFkappaB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.