Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines: a development protocol.

Diagnostic accuracy studies play an important role in informing clinical practice and patient management, by evaluating the ability of diagnostic testing and imaging to identify the presence or absence of a disease or condition. These studies compare the relative diagnostic strength of the test or device with a reference standard, therefore, guiding clinical decisions on the reliability of the test, the need for further tests, and whether to monitor or treat a particular condition. Inadequate and incomplete reporting of diagnostic accuracy studies can disguise methodological deficiencies and ultimately result in study bias and the inability to translate research findings into daily clinical practice. The Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines are being developed in order to improve the accuracy, transparency, completeness and reproducibility of diagnostic accuracy studies in the speciality of Endodontology. The aim of this paper is to report the process used to develop the PRIDASE guidelines based on a well-established consensus process. The project leaders (PD, VN) formed a steering committee of nine members (PD, VN, PA, AF, DR, SP, CK, MP, HD) to oversee and manage the project. The PRIDASE steering committee will develop the initial draft of the PRIDASE guidelines by adapting and modifying the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines, adding new items related specifically to the nature of Endodontics and incorporate the Clinical and Laboratory Images in Publication (CLIP) principles. The initial guidelines will consist of a series of domains and individual items and will be validated by the members of a PRIDASE Delphi Group (PDG) consisting of a minimum of 30 individuals who will evaluate independently the individual items based on two parameters: 'clarity' using a dichotomous scoring (yes/no) and 'suitability' for inclusion using a 9-point Likert Scale. The scores awarded by each member and any suggestions for improvement will be shared with the PDG to inform an iterative process that will result in a series of items that are clear and suitable for inclusion in the new PRIDASE guidelines. Once the PDG has completed its work, the steering committee will create a PRIDASE Meeting Group (PMG) of 20 individuals from around the world. Members of the PDG will be eligible to be the part of PMG. The draft guidelines and flowchart approved by the PDG will then be presented for further validation and agreement by the PMG. As a result of these discussions, the PRIDASE guidelines will be finalized and then disseminated to relevant stakeholders through publications and via the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org). Periodic updates to the PRIDASE guidelines will be made based on feedback from stakeholders and end-users.

Frequency of additional treatments in relation to the number of root filled canals in molar teeth in the Swedish adult population.

AIM: To investigate the 5-year frequency of additional treatments in relation to the number of reported root filled canals in molar teeth in Sweden. METHODOLOGY: The cohort included first and second molars in adult individuals who were registered with a root filling performed in 2009. Treatment codes corresponding to root fillings of teeth with from one up to four root filled canals were identified in the Swedish Social Insurance Agency database. The studied additional treatments were extraction, non-surgical root canal retreatment and endodontic surgery during the subsequent 5 years, identified by corresponding codes for these treatments registered on these specific teeth. Differences in the frequency of additional treatments based on the number of root filled canals were analysed using chi-square test and considered statistically significant at P < 0.05. RESULTS: In 2009, root fillings on a first or second molar tooth were registered in 100 720 individuals. The study included 32 901 maxillary first molars (6.4% with four root filled canals), 12 763 maxillary second molars (3.3% with four root filled canals), 37 703 mandibular first molars (19.2% with four root filled canals) and 17 353 mandibular second molars (3.7% with four root filled canals). The total frequency of additional treatments was 14.3% (n = 14 425) during the 5-year observational period. Additional treatments were more frequent in teeth with 1-3 root filled canals compared to teeth with four root filled canals for maxillary first molars (15.2% vs. 12.7%, P = 0.002), maxillary second molars (13.8% vs. 9.1%, P = 0.007) and mandibular first molars (14.0% vs. 10.7%, P < 0.001) but not mandibular second molars (15.6% vs. 13.7%, P = 0.200). CONCLUSIONS: Over 5 years, 85.7% of the included teeth were not registered with any additional treatments. Maxillary first and second molars and mandibular first molar teeth had a greater frequency of additional treatments when ≤3 root canals were filled compared to four canals.

Preferred Reporting items for OBservational studies in Endodontics (PROBE) guidelines: a development protocol.

Observational studies have a significant role in establishing the prevalence and incidence of diseases in populations, as well as determining the benefits and risks associated with health-related interventions. Observational studies principally encompass cohort, case-control, case series and cross-sectional designs. Inadequate reporting of observational studies is likely to have a negative impact on decision-making in day-to-day clinical practice; however, no reporting guidelines have been published for observational studies in Endodontics. The aim of this project is to develop reporting guidelines for authors when creating manuscripts describing observational studies in the field of Endodontology in an attempt to improve the quality of publications. The new guidelines for observational studies will be named: 'Preferred Reporting items for OBservational studies in Endodontics (PROBE)'. A steering committee was formed by the project leaders (PD, VN) to develop the guidelines through a five-phase consensus process. The steering committee will review and adapt items from the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement and the Clinical and Laboratory Images in Publications (CLIP) principles, as well as identify new items that add value to Endodontics. The steering committee will create a PROBE Delphi Group (PDG), consisting of 30 members across the globe to review and refine the draft checklist items and flowchart. The items will be assessed by the PDG on a nine-point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PROBE Face-to-Face meeting group (PFMG) made up of 20 individuals to further refine the guidelines. After receiving feedback from the PFMG, the steering committee will pilot and finalize the guidelines. The approved PROBE guidelines will be disseminated through publication in relevant journals, and be presented at national and international conferences. The PROBE checklist and flowchart will be available and downloadable from the Preferred Reporting Items for study Designs in Endodontics (PRIDE) website: www.pride-endodonticguidelines.org. The PROBE steering committee encourages clinicians, researchers, editors and peer reviewers to provide feedback on the PROBE guidelines to inform the steering group when the guidelines are updated.

PRIRATE 2020 guidelines for reporting randomized trials in Endodontics: a consensus-based development.

In evidence-based health care, randomized clinical trials provide the most accurate and reliable information on the effectiveness of an intervention. This project aimed to develop reporting guidelines, exclusively for randomized clinical trials in the dental specialty of Endodontology, using a well-documented, validated consensus-based methodology. The guidelines have been named Preferred Reporting Items for RAndomized Trials in Endodontics (PRIRATE) 2020. A total of eight individuals (PD, VN, HD, LB, TK, JJ, EP and SP), including the project leaders (PD and VN) formed a steering committee. The committee developed a checklist based on the items in the Consolidated Standards of Reporting Trials (CONSORT) guidelines and Clinical and Laboratory Images in Publications (CLIP) principles. A PRIRATE Delphi Group (PDG) and PRIRATE Face-to-Face Meeting group (PFMG) were also formed. Thirty PDG members participated in the online Delphi process and achieved consensus on the checklist items and flowchart that make up the PRIRATE guidelines. The guidelines were discussed at a meeting of the PFMG at the 19th European Society of Endodontology (ESE) Biennial congress, held on 13 September 2019 in Vienna, Austria. A total of 21 individuals from across the globe and four steering committee members (PD, VN, HD and LB) attended the meeting. As a consequence of the discussions, the guidelines were modified and then piloted by several authors whilst writing a manuscript. The PRIRATE 2020 guidelines contain a checklist consisting of 11 sections and 58 individual items as well as a flowchart, considered essential for authors to include when writing manuscripts for randomized clinical trials in Endodontics.

How May Placebo Mechanisms Influence Orofacial Neuropathic Pain?

The conceptualization of placebo has changed from inactive pills to a detailed understanding of how patients' perception of receiving a treatment influences pain processing and overall treatment outcome. Large placebo effects were recently demonstrated in chronic neuropathic pain, thereby opening the question of whether placebo effects also apply to orofacial neuropathic pain. In this article, we review the new definitions, magnitude, and social, psychological, neurobiologic, and genetic mechanisms of placebo effects in pain, especially neuropathic pain, to illustrate that placebo effects are not simply response bias but psychoneurobiological phenomena that can be measured at many levels of the neuroaxis. We use this knowledge to carefully illustrate how patients' perceptions of the treatment, the relationship with the health care provider, and the expectations and emotions toward a treatment can influence test and treatment outcome and potentially skew the results if they are not taken into consideration. Orofacial neuropathic pain is a new research area, and we review the status on definition, diagnosis, mechanisms, and pharmacologic treatment of neuropathic pain after trigeminal nerve injury, as this condition may be especially influenced by placebo factors. Finally, we have a detailed discussion of how knowledge of placebo mechanisms may help improve the understanding, diagnosis, and treatment of orofacial neuropathic pain, and we illustrate pitfalls and opportunities of applying this knowledge to the test of dental treatments.

The frequency and characteristics of pain and discomfort associated with root filled teeth: a practice-based study.

AIM: To (i) investigate the frequency and characteristics of pain and discomfort associated with root filled teeth in adult patients regularly attending the Public Dental Service in Örebro County, Sweden; (ii) assess the association between symptoms and clinical and radiographic findings; and (iii) explore the impact of pain and discomfort from root filled teeth on daily life. METHODOLOGY: Patient records of adult patients (≥20 years) scheduled for routine check-ups in April 2015 were screened to identify individuals with root filled teeth; all patients with ≥1 root filled tooth were asked to participate. The examination comprised of clinical and radiographic examinations and questionnaires on general health, on pain symptoms from root filled teeth and on the impact of pain on daily activities. In a general estimating equation (GEE), examination findings and patient-related factors were independently analysed in relation to the outcome 'presence of pain'. RESULTS: In total, 550 patients with 1256 root filled teeth participated. Fifty-three patients (9.6%) experienced pain or discomfort from 62 (4.9%) root filled teeth. Lower age, percussion tenderness and apical tenderness were significantly associated with pain (P > 0.001 to P = 0.044). The average pain intensity was 2.1 on a (0-10) Numeric Rating Scale, and average duration was 28.4 months. The impact on daily life was low. CONCLUSIONS: On average, pain associated with root filled teeth was of mild intensity, >2 years of duration and had low impact on daily life. Although the significantly associated clinical findings may indicate apical periodontitis as the most probable explanation in some teeth, the origin of pain from root filled teeth remains partly unexplained.

Clinical diagnosis of temporomandibular joint arthritis.

Evidence-based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push-pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL-1ß, IL-1ra, IL-1sRII, IL-6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non-arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.

Reliability of intra-oral quantitative sensory testing (QST) in patients with atypical odontalgia and healthy controls - a multicentre study.

The reliability of comprehensive intra-oral quantitative sensory testing (QST) protocol has not been examined systematically in patients with chronic oro-facial pain. The aim of the present multicentre study was to examine test-retest and interexaminer reliability of intra-oral QST measures in terms of absolute values and z-scores as well as within-session coefficients of variation (CV) values in patients with atypical odontalgia (AO) and healthy pain-free controls. Forty-five patients with AO and 68 healthy controls were subjected to bilateral intra-oral gingival QST and unilateral extratrigeminal QST (thenar) on three occasions (twice on 1 day by two different examiners and once approximately 1 week later by one of the examiners). Intra-class correlation coefficients and kappa values for interexaminer and test-retest reliability were computed. Most of the standardised intra-oral QST measures showed fair to excellent interexaminer (9-12 of 13 measures) and test-retest (7-11 of 13 measures) reliability. Furthermore, no robust differences in reliability measures or within-session variability (CV) were detected between patients with AO and the healthy reference group. These reliability results in chronic orofacial pain patients support earlier suggestions based on data from healthy subjects that intra-oral QST is sufficiently reliable for use as a part of a comprehensive evaluation of patients with somatosensory disturbances or neuropathic pain in the trigeminal region.

A Scandinavian case of skin fragility, alopecia and cardiomyopathy caused by DSP mutations.

Congenital skin fragility is a heterogeneous disorder with epidermolysis bullosa and various skin infections as the leading causes. However, even rare diseases must be considered in the differential diagnosis of neonatal skin blistering, including some genetic syndromes with extracutaneous involvement. One such syndrome is ectodermal dysplasia due to deficiency of desmoplakin, a desmosomal protein essential for cellular cohesion in both epithelia and cardiac tissues. Desmoplakin is encoded by the DSP gene, which is localized on chromosome 6p24. Both dominant and recessive mutations in this gene have been reported to cause skin fragility and keratinization defects. We report a child born with a fragile epidermis, alopecia, thick nails, and focal hyperkeratoses on the digits and knees. She was found to have a deficiency of desmoplakin caused by compound heterozygous DSP mutations. She has gradually developed signs of a left ventricular cardiomyopathy.

Diagnostic yield of conventional radiographic and cone-beam computed tomographic images in patients with atypical odontalgia.

AIM: To investigate whether the additional diagnostic yield of a cone-beam computed tomography (CBCT) examination over conventional radiographs in patients primarily suspected of having atypical odontalgia (AO) improves differentiation between AO and symptomatic apical periodontitis (SAP) in patients with severe chronic intraoral pain. METHODOLOGY: In this clinical study, 25 patients (mean age 54 ± 11 years, range 34-72) participated; 20 were diagnosed with AO and 5 with SAP. All patients were recruited from the clinics of the Faculty of Odontology, Malmö University. AO inclusion criteria were chronic pain (>6 months) in a region where a tooth had been endodontically or surgically treated, with no pathological cause detectable in clinical or radiologic examinations. SAP inclusion criteria were recurrent pain from a tooth diagnosed with apical periodontitis in clinical and radiographic examinations. Assessments comprised a self-report questionnaire on pain characteristics, a comprehensive clinical examination and a radiographic examination including panoramic and intraoral radiographs and CBCT images. The main outcome measure was periapical bone destruction. RESULTS: Sixty per cent of patients with AO had no periapical bone destructions detectable with any radiographic method. Overall, CBCT rendered 17% more periapical bone destructions than conventional radiography. Average pain intensity in patients with AO was 5.6 (± 1.8) on a 0-10 numerical rating scale, and average pain duration was 4.3 (± 5.2) years. CONCLUSION: Cone-beam computed tomography improves identification of patients without periapical bone destruction, which may facilitate differentiation between AO and SAP.

Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions--a taskforce report.

The goals of an international taskforce on somatosensory testing established by the Special Interest Group of Oro-facial Pain (SIG-OFP) under the International Association for the Study of Pain (IASP) were to (i) review the literature concerning assessment of somatosensory function in the oro-facial region in terms of techniques and test performance, (ii) provide guidelines for comprehensive and screening examination procedures, and (iii) give recommendations for future development of somatosensory testing specifically in the oro-facial region. Numerous qualitative and quantitative psychophysical techniques have been proposed and used in the description of oro-facial somatosensory function. The selection of technique includes time considerations because the most reliable and accurate methods require multiple repetitions of stimuli. Multiple-stimulus modalities (mechanical, thermal, electrical, chemical) have been applied to study oro-facial somatosensory function. A battery of different test stimuli is needed to obtain comprehensive information about the functional integrity of the various types of afferent nerve fibres. Based on the available literature, the German Neuropathic Pain Network test battery appears suitable for the study of somatosensory function within the oro-facial area as it is based on a wide variety of both qualitative and quantitative assessments of all cutaneous somatosensory modalities. Furthermore, these protocols have been thoroughly described and tested on multiple sites including the facial skin and intra-oral mucosa. Standardisation of both comprehensive and screening examination techniques is likely to improve the diagnostic accuracy and facilitate the understanding of neural mechanisms and somatosensory changes in different oro-facial pain conditions and may help to guide management.

Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes have been identified in ARCI, but the association between genotype and phenotype is poorly understood. METHODS: To investigate genotype-phenotype correlations in ARCI, we selected 27 patients from 18 families with specific ultrastructural features of the epidermis. The characteristic findings using electron microscopy (EM) were abnormal lamellar bodies and elongated membranes in the stratum granulosum, classified as ARCI EM type III. DNA samples from a subset of affected individuals were screened for homozygous genomic regions, and a candidate gene region was identified on chromosome 5q33. The region coincides with the ichthyin gene, previously reported as mutated in ARCI. RESULTS: Mutation screening of ichthyin revealed missense or splice-site mutations in affected members from 16 of 18 (89%) families with characteristics of ARCI EM type III. In a control group of 18 patients with ARCI without EM findings consistent with type III, we identified one patient homozygous for a missense mutation in ichthyin. DISCUSSION: Our findings indicate a strong association between ultrastructural abnormalities in the granular layer of epidermis and ichthyin mutations. The results also suggest that EM provides a tool for specific diagnosis in a genetically homogenous subgroup of patients with ARCI.

Fatal bleeding following delivery: a manifestation of the vascular type of Ehlers-Danlos' syndrome.

INTRODUCTION: The vascular form of Ehlers-Danlos' syndrome (type IV) is a potentially lethal genetic condition because of rupture of major arteries, often in the peri-partum period. CASE REPORT: We report a 31-year-old primipara who died from a rupture of the right subclavian artery. The patient had several symptoms and signs typical of the disease. The rupture occurred during the expulsion-phase of delivery but was recognized only on day 9. CONCLUSION: Early recognition is crucial to avoid maternal mortality due to this genetic disorder. Once the condition is suspected, the clinical diagnosis is straightforward.

A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by haplotype association.

Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs). Allelic association, evaluated with Fisher's exact test and P (excess), was used to refine the IPS haplotype to approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS patients, we calculated the age of a founder mutation to approximately 1,900 years. The IPS haplotype contains a core region of 76 kb consisting of four marker alleles shared by 97.7% of the chromosomes associated with IPS. This region spans four known genes, all of which are expressed in mature epidermal cells. We present the results from the analysis of these four genes and their corresponding transcripts in normal and patient-derived samples.

Haplotype association and mutation analysis of the transglutaminase 1 gene for prenatal exclusion of lamellar ichthyosis.

Lamellar ichthyosis (LI) is an autosomal recessive keratinization disorder of the skin. Genetic heterogeneity has been shown for the disease and there is evidence for the involvement of the transglutaminase 1 (TGM1) gene on chromosome 14q11. We have previously identified chromosome 14q11 haplotypes associated with ichthyosis in the Norwegian population. In this paper we describe antenatal exclusion of ichthyosis in two Norwegian families by chromosome 14q11 haplotype association and direct mutation analysis. In one pregnancy, the 11-week old fetus at risk for LI was found to share only one disease-associated haplotype. A subsequent mutation analysis of the TGM1 gene in fetal DNA revealed that the fetus carried a novel 3795A-->T transversion. The affected proband was compound heterozygous for the mutations 3795A-->T and 3239G-->C resulting in an Asp430Val and a Val379Leu, respectively. In another LI family, the 11-week old fetus was found to be heterozygous for the 14q11 haplotype associated with the disease. Subsequent mutation analysis revealed that the fetus was heterozygous for the 2526A-->G transition in the splice site of intron 5 whereas the proband was homozygous for the same mutation. Our results show that haplotyping can be a useful tool for prenatal diagnosis in diseases with genetic heterogeneity.

Further evidence of genetic homogeneity in Sjögren-Larsson syndrome.

Sjögren-Larsson syndrome is an autosomal recessive disorder characterized by congenital ichthyosis, spastic di- or tetraplegia and mental retardation. In 1994 Sjögren-Larsson syndrome was mapped to chromosome 17, close to the genetic marker D17S805 in a study of 24 Swedish families. We have analysed 12 microsatellite markers in 10 additional non-Swedish families with Sjögren-Larsson syndrome originating from Germany, Lebanon, Spain and Canada. The results are consistent with earlier data and give further evidence of Sjogren-Larsson syndrome being a homogeneous disorder. Swedish soldiers were bivouacking in Germany during the 30-year war in the 17th century and it has been suggested that they could have introduced the Sjögren-Larsson syndrome gene to the German population. Haplotypes from 7 German families with Sjögren-Larsson syndrome were compared with earlier analysed Swedish haplotypes. No evidence of all German patients carrying the same mutation or the major "Swedish Sjögren-Larsson syndrome gene" was found.

Detailed genetic and physical mapping in the Sjögren-Larsson syndrome gene region in 17p11.2.

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder characterised by mental retardation, spasticity, and ichthyosis. In 1994, SLS was linked to chromosome 17 and the gene causing the disorder was recently identified as fatty aldehyde dehydrogenase (FALDH) located in 17p11.2. In this paper we present a detailed genetic and physical map of the region surrounding the SLS/FALDH locus, produced by using new microsatellite markers analysed on the extensive Swedish family material, a radiation hybrid panel, and yeast artificial chromosomes (YACs).

Strong founder effect for a transglutaminase 1 gene mutation in lamellar ichthyosis and congenital ichthyosiform erythroderma from Norway.

Autosomal recessive congenital ichthyosis (ARCI) is a clinically heterogeneous disorder of keratinisation. It was recently shown that mutations in the transglutaminase 1 (TGM1) gene may be associated with the clinical subtypes lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (CIE). Thirty-six Norwegian families with LI and seven with non-bullous CIE were studied with microsatellite markers linked to the TGMI gene. One common haplotype for two markers was found on 74% of disease associated chromosomes. Three individuals homozygous for the common haplotype, two affected by LI and one affected by CIE, were analysed for mutations in the TGM1 gene. All three patients were found homozygous for a single A to G transition located in the canonical splice acceptor site of intron 5. Probands from the remaining 40 families with LI and CIE were screened for this mutation and the A to G transition was found on 61 out of 72 alleles associated with LI and on 9 out of 15 alleles associated with CIE. These findings suggest a single founder mutation for the majority of patients with LI and CIE in Norway. The 2526A-->G mutation results in the insertion of a guanosine at position 877 (876insG) in the mature cDNA and the frame shift creates a premature termination at codon 293. The mutation was previously observed in one family with a resulting cDNA that included the entire intron 5. These results suggest that the mutation can result in variant transcripts in different individuals.