[The assessment of the endodontic foundation]. / De beoordeling van het endodontische fundament.

The diagnosis of an endodontic disease requires thorough research, collecting both clinical and radiographic information. The clinical examination includes history taking, visual inspection of the tooth and surrounding tissues, palpation of the soft and hard tissues, periodontal examination and percussion. The radiographic examination provides valuable information, but can never stand alone in arriving at a diagnosis. It is important to link the findings of the radiographic examination to other information. Sometimes, invasive examination is necessary, during which the coronal restoration is removed to allow better assessment of the tooth. This can provide additional information about the presence of caries, fractures, leakage of the restoration or other reasons for failure of the initial root canal treatment. A good diagnosis is essential for planning successful follow-up treatment.

Locating saddle points using gradient extremals on manifolds adaptively revealed as point clouds.

Steady states are invaluable in the study of dynamical systems. High-dimensional dynamical systems, due to separation of time scales, often evolve toward a lower dimensional manifold M. We introduce an approach to locate saddle points (and other fixed points) that utilizes gradient extremals on such a priori unknown (Riemannian) manifolds, defined by adaptively sampled point clouds, with local coordinates discovered on-the-fly through manifold learning. The technique, which efficiently biases the dynamical system along a curve (as opposed to exhaustively exploring the state space), requires knowledge of a single minimum and the ability to sample around an arbitrary point. We demonstrate the effectiveness of the technique on the Müller-Brown potential mapped onto an unknown surface (namely, a sphere). Previous work employed a similar algorithmic framework to find saddle points using Newton trajectories and gentlest ascent dynamics; we, therefore, also offer a brief comparison with these methods.

Trends, determinants and differences in antibiotic use in 68 residential aged care homes in Australia, 2014-2017: a longitudinal analysis of electronic health record data.

BACKGROUND: Internationally, point prevalence surveys are the main source of antibiotic use data in residential aged care (RAC). Our objective was to describe temporal trends in antibiotic use and antibiotics flagged for restricted use, resident characteristics associated with use, and variation in use by RAC home, using electronic health record data. METHODS: We conducted a retrospective cohort study of 9793 unique residents aged ≥65 years in 68 RAC homes between September 2014 and September 2017, using electronic health records. We modelled the primary outcome of days of antibiotic therapy /1000 resident days (DOT/1000 days), and secondary outcomes of number of courses/1000 days and the annual prevalence of antibiotic use. Antibiotic use was examined for all antibiotics and antibiotics on the World Health Organization's (WHO) Watch List (i.e. antibiotics flagged for restricted use). RESULTS: In 2017, there were 85 DOT/1000 days (99% CI: 79, 92), 8.0 courses/1000 days (99% CI: 7.6, 8.5), and 63.4% (99% CI: 61.9, 65.0) of residents received at least one course of antibiotics. There were 7.7 DOT/1000 days (99% CI: 6.69, 8.77) of antibiotics on the WHO Watch List administered in 2017. Antibiotic use increased annually by 4.09 DOT/1000 days (99% CI: 1.18, 6.99) before adjusting for resident factors, and 3.12 DOT/1000 days (99% CI: - 0.05, 6.29) after adjustment. Annual prevalence of antibiotic use decreased from 68.4% (99% CI: 66.9, 69.9) in 2015 to 63.4% (99% CI: 61.9, 65.0) in 2017, suggesting fewer residents were on antibiotics, but using them for longer. Resident factors associated with higher use were increasing age; chronic respiratory disease; a history of urinary tract infections, and skin and soft tissue infections; but dementia was associated with lower use. RAC home level antibiotic use ranged between 44.0 to 169.2 DOT/1000 days in 2016. Adjusting for resident factors marginally reduced this range (42.6 to 155.5 DOT/1000 days). CONCLUSIONS: Antibiotic course length and RAC homes with high use should be a focus of antimicrobial stewardship interventions. Practices in RAC homes with low use could inform interventions and warrant further investigation. This study provides a model for using electronic health records as a data source for antibiotic use surveillance in RAC.

Serum HBsAg kinetics and usefulness of interferon-inducible protein 10 serum in HBeAg-negative chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

The kinetics of serum HBsAg and interferon-inducible protein 10 (IP10) levels in patients with chronic hepatitis B infection treated with tenofovir are unclear. We evaluated the changes of HBsAg levels and the predictability of IP10 for HBsAg decline in 160 HBeAg-negative patients receiving tenofovir for ≥12 months. Serum samples taken before and at 6, 12, 24, 36 and 48 months after tenofovir were tested for HBsAg levels. In 104 patients, serum samples before tenofovir were tested for IP10 levels. Compared to before tenofovir, HBsAg levels decreased by a median of 0.08, 0.11, 0.24, 0.33 and 0.38 log10 IU/mL at 6, 12, 24, 36 and 48 months, respectively (P < 0.001). HBsAg kinetics did not differ between nucleos(t)ide analogue(s) naive and experienced patients. The 12-, 24-, 36- and 48-month cumulative rates of ≥0.5 log10 HBsAg decline were 8%, 16%, 24% and 41% and of HBsAg ≤100 IU/mL were 9%, 12%, 14% and 18%, respectively. The only factor associated with HBsAg ≤100 IU/mL was lower HBsAg levels before tenofovir (P < 0.001), while HBsAg decline ≥0.5 log10 was associated with higher IP10 levels (P = 0.002) and particularly with IP10 > 350 pg/mL (P < 0.001). In conclusion, tenofovir decreases serum HBsAg levels in both nucleos(t)ide analogue(s) naive and experienced patients with HBeAg-negative chronic hepatitis B infection. After 4 years of therapy, HBsAg ≤100 IU/mL can be achieved in approximately 20% of patients, particularly in those with low baseline HBsAg levels. HBsAg decline is slow (≥0.5 log10 in 40% of patients after 4 years) and is associated only with higher baseline serum IP10 levels.

Litigation associated with intensive care unit treatment in England: an analysis of NHSLA data 1995-2012.

BACKGROUND: The intensive care unit (ICU) is a high-cost high-risk area in which analysis of previous litigation cases may help to improve future practice. METHODS: Claims received by the National Health Service Litigation Authority (NHSLA) relating to ICU, from 1995 to 2012, were analysed according to clinical categories. The severity of outcome was classified as none, low, moderate, severe and death. The cost of the claims were corrected to 2013 values using the retail prices index. RESULTS: Of the 523 claims in the NHSLA dataset, 210 were excluded (as the claims did not relate to ICU care) and 313 were included in the analysis. The commonest claim categories were [number (% of all claims)]: positioning/nursing standards/skin care (mostly relating to pressure sores)- 86 (28%), infection- 79 (26%), respiratory/airway- 63 (20%). The commonest claims relating to patient death were: respiratory/airway (30%), missed/delayed diagnosis (20%) and paediatrics (17%). The claims categories with the highest proportion of severe outcomes were: positioning/nursing standards/skin care (52%) and infection (33%). The total cost of closed claims was £19,973,339. The categories incurring the highest costs were: infection (£6.6 million), positioning/skin care/nursing standards (£4.5 million), delayed/inadequate treatment (£4.3 million). CONCLUSIONS: Litigation arising from care in the ICU is common, costly, and is likely to follow a poor outcome. Whilst the importance of airway/respiratory care and infection control measures are highlighted, the clear prominence of pressure sores in ICU-related litigation is worrisome and represents one particular area for practice improvement.

Nuclear medicine incident reporting in Australia: control charts and notification rates inform quality improvement.

BACKGROUND: Australia has a statutory incident reporting system for radiopharmaceutical maladministrations, but additional research into registry data is required for the purpose of quality improvement in nuclear medicine. AIMS: We (i) used control charts to identify factors contributing to special cause variation (indicating higher than expected rates) in maladministrations and (ii) evaluated the impact of heterogeneous notification criteria and extent of underreporting among jurisdictions and individual facilities, respectively. METHODS: Anonymised summaries of Australian Radiation Incident Register reports permitted calculation of national monthly maladministration notification rates for 2007-2012 and preparation of control charts. Multivariate logistic regression assessed the association of population, insurance and regulatory characteristics with maladministration notifications in each Australian State and Territory. Maladministration notification rates from two facilities with familiarity of notification processes and commitment to radiation protection were compared with those elsewhere. RESULTS: Special cause variation occurred in only 3 months, but contributed to 21% of all incidents (42 of 197 patients), mainly because of 'clusters' of maladministrations (n = 24) arising from errors in bulk radiopharmaceutical dispensing. Maladministration notification rates varied significantly between jurisdictions (0 to 12.2 maladministrations per 100 000 procedures (P < 0.05)) and individual facilities (31.7 vs 5.8 per 100 000; χ(2) = 40; 1 degree of freedom, P < 0.001). CONCLUSIONS: Unexpected increases in maladministration notifications predominantly relate to incident 'clusters' affecting multiple patients. The bulk preparation of radiopharmaceuticals is a vulnerable process and merits additional safeguards. Maladministration notification rates in Australia are heterogeneous. Adopting uniform maladministration notification criteria among States and Territories and methods to overcome underreporting are warranted.

A new type of lordosis and vertebral body compression in Gilthead sea bream, Sparus aurata L.: aetiology, anatomy and consequences for survival.

A new type of vertebral malformation is described, consisting of deformed cartilaginous neural and haemal processes and the compression and fusion of vertebral bodies. The malformation is designated as haemal vertebral compression and fusion (haemal VCF). We studied the aetiology of the malformations and described microanatomical histopathological alterations. The malformations were detected during routine quality control in one of six monitored Gilthead sea bream populations. Haemal VCF affected the posterior part of the vertebral column (haemal vertebrae). In 20% of the deformed specimens, haemal VCF was combined with lordosis. At 35 dph (days post-hatching), early anatomical signs of the haemal VCF consisted of abnormal centrum mineralization, malformed cartilaginous neural and haemal processes and developing lordotic alterations. The histological examination of the deformed individuals revealed that haemal VCF is preceded by notochord abnormalities. The frequency of deformed individuals was three times higher at 35 than at 61 dph (50.3% vs. 17.2%, n = 157 and n = 250, respectively). No signs of repair or reversion of malformations have been observed. Thus, the steep decrease in deformities in older animals suggests that haemal VCF is linked to high mortality rates. The results are discussed in respect of the possible causative factors of haemal VCF.

Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review.

This systematic review delineates the effect of primary therapeutic hypothermia (PTH) (initiated on presentation of the patient) on both mortality and neurological outcome in patients with traumatic brain injury. The safety profile of the therapy is also assessed. A systematic search of the following databases was performed: MEDLINE, EMBASE, Zetoc database of conference proceedings, the Cochrane Database of Systematic Reviews, and the clinicaltrials.gov website, up to July 28, 2011. Relevant journals were hand-searched for further articles and reference lists were checked against the retrieved results for additional resources. The retrieved results were filtered for randomized controlled trials in English where systemic hypothermia was applied for ≥ 12 h in the treatment arm and outcome was assessed at a minimum of 3 months. Randomized controlled trials were assessed for quality of evidence using the GRADE system. Eighteen randomized controlled trials (1851 patients) were identified. The overall relative risk of mortality with PTH when compared with controls was 0.84 [95% confidence interval (CI)=0.72-0.98] and of poor neurological outcome was 0.81 (95% CI=0.73-0.89). However, when only high-quality trials were analysed, the relative risks were 1.28 (95% CI=0.89-1.83) and 1.07 (95% CI=0.92-1.24), respectively. Hypothermia was associated with cerebrovascular disturbances on rewarming and possibly with pneumonia in adult patients. Given the quality of the data currently available, no benefit of PTH on mortality or neurological morbidity could be identified. The therapy should therefore only be used within the confines of well-designed clinical trials.

Difference in general practice telehealth utilisation associated with birth country during COVID-19 from two Australian states.

Objective: Telehealth has been an integral part of ensuring continued general practice access during the COVID-19 pandemic. Whether telehealth was similarly adopted across different ethnic, cultural, and linguistic groups in Australia is unknown. In this study, we assessed how telehealth utilisation differed by birth country. Methods: In this retrospective observational study, electronic health record data from 799 general practices across Victoria and New South Wales, Australia between March 2020 to November 2021 were extracted (12,403,592 encounters from 1,307,192 patients). Multivariate generalised estimating equation models were used to assess the likelihood of a telehealth consultation (against face-to-face consultation) by birth country (relative to Australia or New Zealand born patients), education index, and native language (English versus others). Results: Patients born in Southeastern Asia (aOR: 0.54; 95% CI: 0.52-0.55), Eastern Asia (aOR: 0.63; 95% CI: 0.60-0.66), and India (aOR: 0.64; 95% CI: 0.63-0.66) had a lower likelihood of having a telehealth consultation compared to those born in Australia or New Zealand. Northern America, British Isles, and most European countries did not present with a statistically significant difference. Additionally, higher education levels (aOR: 1.34; 95% CI: 1.26-1.42) was associated with an increase in the likelihood of a telehealth consultation, while being from a non-English-speaking country was associated with a reduced likelihood (aOR: 0.83; 95% CI: 0.81-0.84). Conclusions: This study provides evidence showing differences in telehealth use associated with birth country. Strategies to ensure continued healthcare access for patients, whose native language is not English, such as providing interpreter services for telehealth consultations, would be beneficial. Perspectives: Understanding cultural and linguistic differences may reduce health disparities in telehealth access in Australia and could present an opportunity to promote healthcare access in diverse communities.

Evolution and simplified terminology of natural orifice transluminal endoscopic surgery (NOTES), laparoendoscopic single-site surgery (LESS), and mini-laparoscopy (ML).

INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS) are the next steps in the evolution of laparoscopic surgery, promising reduced morbidity and improved cosmetic result. The inconsistent terminology initially used led to confusion. Understanding the technical evolution, the current status and a unified and simplified terminology are key issues for further acceptance of both approaches. OBJECTIVE: To present LESS and NOTES in its historical context and to clarify the associated terminology. METHOD: Extensive literature search took place using the PubMed. Several hundred publications in general surgery and urology regarding LESS are present including the expert opinion of members the European Society of Uro-technology (ESUT). RESULTS: The increasing interest on NOTES and LESS is reflected by a raising number of publications during the last 4 years. The initial confusion with the terminology of single-incision surgery represented a significant issue for further evolution of the technique. Thus, consortiums of experts searched a universally acceptable name for single-incision surgery. They determined that 'laparoendoscopic single-site surgery' (LESS) was both scientifically accurate and colloquially appropriate, the term being also ratified by the NOTES working group (Endourological Society) and the ESUT. For additional use of instruments, the terms hybrid NOTES and hybrid LESS should be used. Any single use of miniaturized instruments for laparoscopy should be called mini-laparoscopy. DISCUSSION: The evolution of LESS and most likely NOTES to a new standard of minimally invasive surgery could represent an evolutionary step even greater than the one performed by the establishment of laparoscopy over open surgery.

A Scoping Review of Adverse Incidents Research in Aged Care Homes: Learnings, Gaps, and Challenges.

Background: Adverse incidents are well studied within acute care settings, less so within aged care homes. The aim of this scoping review was to define the types of adverse incidents studied in aged care homes and highlight strengths, gaps, and challenges of this research. Methods: An expanded definition of adverse incidents including physical, social, and environmental impacts was used in a scoping review based on the PRISMA Extension for Scoping Reviews Checklist. MEDLINE, CINAHL, and EBSCOhost were searched for English language, peer-reviewed studies conducted in aged care home settings between 2000 and 2020. Forty six articles across 12 countries were identified, charted, and analyzed using descriptive statistics and narrative summary methods. Results: Quantitative studies (n = 42, 91%) dominated adverse incidents literature. The majority of studies focused on physical injuries (n = 29, 63%), with fewer examining personal/interpersonal (15%) and environmental factors (22%). Many studies did not describe the country's aged care system (n = 26, 56%). Only five studies (11%) included residents' voices. Discussion: This review highlights a need for greater focus on resident voices, qualitative research, and interpersonal/environmental perspectives in adverse event research in aged care homes. Addressing these gaps, future research may contribute to better understanding of adverse incidents within this setting.

General practice perspective on the use of telehealth during the COVID-19 pandemic in Australia using an Action Research approach: a qualitative study.

OBJECTIVES: Telehealth has emerged as a viable and safe mode of care delivery in Australia during the COVID-19 pandemic. However, electronic general practice data reveal differences in uptake and consultation mode, which we hypothesise may be due to potential barriers impacting on quality of care. We aimed to identify the benefits and barriers of telehealth use in general practice, using an 'Action Research' approach involving general practitioners (GPs) and general practice stakeholders. DESIGN: Qualitative focus group performed within a broader Action Research methodology. SETTING: A focus group was held in August 2021, with general practice participants from Victoria, Australia. PARTICIPANTS: The study consisted of a purposive sample of 11 participants, including GPs (n=4), representatives from three primary health networks (n=4) and data custodian representatives (n=3) who were part of a project stakeholder group guided by an Action Research approach. METHODS: Semistructured interview questions were used to guide focus group discussions via videoconference, which were recorded and transcribed verbatim for analysis. The transcript was analysed using an inductive thematic approach. RESULTS: Emerging themes included evolution of telehealth, barriers to telehealth (privacy, eligibility, technology, quality of care, sociodemographic and residential aged care barriers) and benefits of telehealth (practice, quality of care, sociodemographic and residential aged care benefits). CONCLUSION: The findings highlight a range of barriers to telehealth that impact general practice, but also provide justification for the continuation and development of telehealth. These results provide important context to support data-driven population-based findings on telehealth uptake. They also highlight areas of quality improvement for the enhancement of telehealth as a valuable tool for routine general practice patient care.

A rare case of adrenal extramedullary haematopoiesis in a Cypriot woman with ß-thalassaemia.

We report a rare case of adrenal extramedullary haematopoiesis (EMH) in a thalassaemia patient in Cyprus. A 40-year-old woman with ß-thalassaemia presented with a 2-day history of non-specific right-sided abdominal pain on routine follow-up for her thalassaemia treatment. Her laboratory tests were not dissimilar to her routine results and no palpable mass was detected. Computed tomography findings revealed a 5.8×4.2×4.6cm solid lesion in the right adrenal gland. Surgical excision was advised for this symptomatic large tumour with the possibility of malignancy in a young patient, and a laparoscopic adrenalectomy was performed. Postoperative follow-up was uneventful. A review of the literature in PubMed and MEDLINE revealed 14 case reports worldwide with adrenal EMH secondary to ß-thalassaemia. EMH tumours in patients with thalassaemia have been reported incidentally, which stresses the importance of considering this in the list of differentials of adrenal incidentalomas in this patient population.

Cue utilisation reduces the impact of response bias in histopathology.

Histopathologists make diagnostic decisions that are thought to be based on pattern recognition, likely informed by cue-based associations formed in memory, a process known as cue utilisation. Typically, the cases presented to the histopathologist have already been classified as 'abnormal' by clinical examination and/or other diagnostic tests. This results in a high disease prevalence, the potential for 'abnormality priming', and a response bias leading to false positives on normal cases. This study investigated whether higher cue utilisation is associated with a reduction in positive response bias in the diagnostic decisions of histopathologists. Data were collected from eighty-two histopathologists who completed a series of demographic and experience-related questions and the histopathology edition of the Expert Intensive Skills Evaluation 2.0 (EXPERTise 2.0) to establish behavioural indicators of context-related cue utilisation. They also completed a separate, diagnostic task comprising breast histopathology images where the frequency of abnormality was manipulated to create a high disease prevalence context for diagnostic decisions relating to normal tissue. Participants were assigned to higher or lower cue utilisation groups based on their performance on EXPERTise 2.0. When the effects of experience were controlled, higher cue utilisation was specifically associated with a greater accuracy classifying normal images, recording a lower positive response bias. This study suggests that cue utilisation may play a protective role against response biases in histopathology settings.

Operative outcomes for wide awake local anesthesia versus regional and general anesthesia for flexor tendon repair.

Operative repair of flexor tendons after traumatic injury may be performed under general anesthesia (GA), regional blocks, or a wide-awake local anesthesia no tourniquet (WALANT) technique. To our knowledge there are currently no large-scale reports evaluating outcomes of flexor tendon repair in patients where wide-awake anesthesia was utilized in comparison to regional anesthesia (RA) and general anesthesia. We performed a retrospective analysis of patients who underwent treatment for flexor tendon injuries at a tertiary referral center for hand surgery over a two-year period. A total of 151 patients were included (53 WALANT, 57 RA, and 41 GA) and a total of 251 tendons were repaired (63 WALANT, 104 RA and 84 GA). No statistically significant difference was observed in rates of tendon rupture, adhesions, infection, or hand function. Flexor tendon repair under WALANT is found to be safe and presents comparable operative and functional outcomes to more traditional anesthetic techniques. Additional advantages, including the ability to test the repair intraoperatively, patient education, and the potential for boosting theatre efficiency. Further studies, preferably utilizing a randomized trial methodology, may further elucidate the benefits and risks of WALANT versus regional and general anesthesia.

Proteomics analysis of epithelial cells reprogrammed in cell-free extract.

The functional reprogramming of a differentiated cell to a pluripotent state presents potential beneficial applications in regenerative medicine. We report here the proteomic profile of 293T epithelial cells reprogrammed to a pluripotent state using undifferentiated embryonal carcinoma (NCCIT) cellular extracts. 293T cells were reversibly permeabilized with streptolysin O, incubated in an extract of NCCIT cells or a control extract of 293T cells for 1 h, resealed with CaCl(2), and cultured. OCT4 and SOX2 gene expression were up-regulated in NCCIT extract-treated cells relative to control cells, whereas there was no alteration in DNMT3B gene expression. Thirty percent of NCCIT extract-treated cells were positive for SSEA-4, and karyotyping confirmed their 293T origin, excluding the possibility of contamination from NCCIT cells. Two-dimensional PAGE revealed approximately 400 protein spots for each cell type studied. At least 10 protein spots in the proteome of NCCIT extract-treated cells had an expression profile similar to that of NCCIT and remained unaltered in control cells. Using tandem mass spectrometry, we identified these proteins, which include 78-kDa glucose-regulated protein precursor and tropomyosin alpha-3 chain. This investigation provides the first evidence that proteins are altered in a specific manner in NCCIT extract-treated cells. This is the first report on the proteomic characterization of the nuclear reprogramming process.

Effects of complement component 3 derivatives on pig oocyte maturation, fertilization and early embryo development in vitro.

Complement component 3 (C3) has well-established roles within immune system, but its roles outside of immune system are less characterized. The extensive presence of C3 throughout the female reproductive tract, and its temporal, and gamete-specific regulation of expression suggest a potential role for C3 in reproduction. In the present investigation, the effects of C3, C3b and iC3b on porcine oocyte maturation, fertilization and embryonic development were examined. We identified the ability of iC3b to positively influence oocyte maturation. No effects on fertilization efficiency, penetration rates, polyspermy and blastocyst formation were observed. However, C3, C3b and iC3b presence in embryo culture medium resulted in fewer total cells in test blastocysts compared to control blastocysts. The results of this study indicate a potential function for iC3b in oocyte maturation. Furthermore, it was demonstrated that the presence of either C3, C3b or iC3b has a negative influence on early embryonic development in the porcine species.

Influence of serum iron test results on the diagnosis of iron deficiency in children: a retrospective observational study.

BACKGROUND AND OBJECTIVE: Serum iron results are not indicative of iron deficiency yet may be incorrectly used to diagnose iron deficiency instead of serum ferritin results. Our objective was to determine the association between serum iron test results and iron-deficiency diagnosis in children by general practitioners. DESIGN, SETTING, PATIENTS AND MAIN OUTCOME MEASURES: A retrospective observational study of 14 187 children aged 1-18 years with serum ferritin and serum iron test results from 137 general practices in Victoria, Australia, between 2008 and 2018. Generalised estimating equation models calculating ORs were used to determine the association between serum iron test results (main exposure measure) and iron-deficiency diagnosis (outcome measure) in the following two population groups: (1) iron-deplete population, defined as having a serum ferritin <12 µg/L if aged <5 years and <15 µg/L if aged ≥5 years and (2) iron-replete population, defined as having a serum ferritin >30 µg/L. RESULTS: 3484 tests were iron deplete and 15 528 were iron replete. Iron-deplete children were less likely to be diagnosed with iron deficiency if they had normal serum iron levels (adjusted OR (AOR): 0.73; 95% CI 0.57 to 0.96). Iron-replete children had greater odds of an iron-deficiency diagnosis if they had low serum iron results (AOR: 2.59; 95% CI 1.72 to 3.89). Other contributors to an iron-deficiency diagnosis were female sex and having anaemia. CONCLUSION: Serum ferritin alone remains the best means of diagnosing iron deficiency. Reliance on serum iron test results by general practitioners is leading to significant overdiagnosis and underdiagnosis of iron deficiency in children.

Reactive oxygen species can be traced locally and systemically in apical periodontitis: A systematic review.

OBJECTIVES: The aim of this systematic review was to summarize the existing evidence on the local production and systemic traces of reactive oxygen species (ROS) in apical periodontitis (AP). DESIGN: A search of MEDLINE-PubMed and EMBASE was conducted up to January 12 of 2021 to identify studies in 6 different languages. Eligibility was evaluated and data were extracted from the eligible studies following the predefined objective. The Newcastle-Ottawa Scale was used for quality assessment of the included studies. RESULTS: After screening, 21 papers met the inclusion criteria. Six studies were about systemic oxidative stress, 14 studies examined local production of reactive oxygen species and one studied both. ROS modulate cell signalling and cause oxidant imbalance locally at the site of AP. Cell signalling leads to a pro-inflammatory response, activation of MMPs and formation and progression of the AP lesion. Simultaneously, these oxidative stress biomarkers are also found in blood and saliva of subjects with AP. CONCLUSIONS: Understanding the mechanism of ROS generation, involved in chronic inflammation, can provide us with important information to enhance local and systemic healing and possibly improve diagnostic tools. Future research considerations would be to use antioxidants to accelerate the return to oxidative balance.

The influence of apical periodontitis on the concentration of inflammatory mediators in peripheral blood plasma and the metagenomic profiling of endodontic infections: Study design and protocol.

Increased systemic inflammation has been identified in presence of oral disease, specifically endodontic disease. It is important to investigate whether treatment of the oral disease ameliorates systemic inflammation. Furthermore, there is no information about the extent to which different microorganisms may trigger inflammatory response. OBJECTIVES: Primarily (i) to compare the plasma concentrations of inflammatory mediators of apical periodontitis (AP) subjects to controls, (ii) to evaluate whether elimination of the endodontic infection reduces systemic inflammation (iii) to investigate the microbiome of root canal infections. Secondarily i) to correlate the inflammatory mediator data with the microbiome data to investigate whether the type of infection influences the type and severity of the inflammatory condition ii) to examine patterns in the inflammatory mediator data before and after tooth extraction in order to establish a biomarker signature of AP/oral disease.This is a multi-centre prospective case-control intervention study. The cohort will consist of 30 healthy human volunteers with one or two teeth with a root-tip inflammation and 30 matched healthy controls. Peripheral blood will be drawn at 6 time points, 3 before and 3 after the extraction of the tooth with apical periodontitis. The teeth will be pulverized, DNA extraction and sequencing will be performed.This study aims to compare the concentration of inflammatory blood plasma proteins in between AP-subjects and controls at different time points before and after the tooth extraction in a systematic and complete way. Additionally the composition of the root canal microbiome in association with the inflammatory response of the host will be assessed.