Riccia (Ricciaceae) is a widespread, cosmopolitan genus of thalloid liverworts. Here we document the presence of R. cavernosa Hoffm. in New Zealand for the first time. A full description based on New ...Zealand specimens is provided. Riccia cavernosa was discovered in New Zealand in February 2016 growing on the margins of a series of artificial wetlands constructed to aid in the recovery of a threatened endemic wading bird (Himantopus novaezelandiae). Following a review of the status of R. cavernosa in New Zealand we conclude that the species is most likely a recent natural, long distance trans-Tasman wind-dispersed arrival from Australia where the species is locally common. The discovery increases the number of Riccia reported from New Zealand from 10 to 11. Prior to the discovery of R. cavernosa, only four of the 10 Riccia recorded from New Zealand were considered indigenous. The conservation status of R. cavernosa is briefly discussed and a provisional assessment of 'Threatened/Nationally Critical' assigned to the species using the New Zealand Threat Classification System.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The cosmopolitan genus Herbertus is notorious for having a difficult taxonomy and for the fact that there is limited knowledge of species ranges and relationships. Topologies generated from variable ...molecular markers are used to discuss biogeographical patterns in Herbertus and to compare them with the geological history of continents and outcomes reported for other land plants. Africa, Asia, Azores, Europe, southern South America, northern South America, North America, New Zealand. Phylogenetic analyses of nuclear ribosomal internal transcribed spacer and chloroplast (cp) trnL-trnF sequences of 66 accessions of Herbertus and the outgroup species Triandrophyllum subtrifidum and Mastigophora diclados were used to investigate biogeographical patterns in Herbertus. Areas of putative endemism were defined based on the distribution of species included in the analyses. Maximum parsimony analyses were undertaken to reconstruct ancestral areas and intraspecies migration routes. The analyses reveal species-level cladograms with a correlation between genetic variation and the geographical distribution of the related accessions. The southern South American Herbertus runcinatus is sister to the remainder of the genus, which is split into two main clades. One contains the Neotropical-African Herbertus juniperoideus and the New Zealand/Tasmanian Herbertus oldfieldianus. An African accession of H. juniperoideus is nested within Neotropical accessions. The second main clade includes species that inhabit Asia, the Holarctic, Africa, and northern South America. Maximum parsimony analyses indicate that this clade arose in Asia. Herbertus sendtneri originated in Asia and subsequently colonized the Holarctic and northern South America. An Asian origin and colonization into Africa is indicated for H. dicranus. The current distribution of Herbertus cannot be explained by Gondwanan vicariance. A more feasible explanation of the range is a combination of short-distance dispersal, rare long-distance dispersal events (especially into regions that faced floral displacements as a result of climatic changes) extinction, recolonization, and diversification. The African Herbertus flora is a mixture of Asian and Neotropical elements. Southern South America harbours an isolated species. The molecular data indicate partial decoupling of molecular and morphological variation in Herbertus. Biogeographical patterns in Herbertus are not dissimilar to those of other groups of bryophytes, but elucidation of the geographical ranges requires a molecular approach. Some patterns could be the result of maintenance of Herbertus in the inner Tropics during glacial maxima, and dispersal into temperate regions in warm phases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less ...frequently used in oropharyngeal cancer. Surgery alone may be treatment for early‐stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. This is an update of a review originally published in 2007 and first updated in 2011.
Objectives
To determine which surgical treatment modalities for oral and oropharyngeal cancers result in increased overall survival, disease‐free survival and locoregional control and reduced recurrence. To determine the implication of treatment modalities in terms of morbidity, quality of life, costs, hospital days of treatment, complications and harms.
Search methods
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE Ovid (1946 to 20 December 2017) and Embase Ovid (1980 to 20 December 2017). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on the language or date of publication.
Selection criteria
Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, or where separate data could be extracted for these participants, and that compared two or more surgical treatment modalities, or surgery versus other treatment modalities.
Data collection and analysis
Two or more review authors independently extracted data and assessed risk of bias. We contacted study authors for additional information as required. We collected adverse events data from included studies.
Main results
We identified five new trials in this update, bringing the total number of included trials to 12 (2300 participants; 2148 with cancers of the oral cavity). We assessed four trials at high risk of bias, and eight at unclear. None of the included trials compared different surgical approaches for the excision of the primary tumour. We grouped the trials into seven main comparisons.
Future research may change the findings as there is only very low‐certainty evidence available for all results.
Five trials compared elective neck dissection (ND) with therapeutic (delayed) ND in participants with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow‐up made meta‐analysis inappropriate in most cases. Four of these trials reported overall and disease‐free survival. The meta‐analyses of two trials found no evidence of either intervention leading to greater overall survival (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.41 to 1.72; 571 participants), or disease‐free survival (HR 0.73, 95% CI 0.25 to 2.11; 571 participants), but one trial found a benefit for elective supraomohyoid ND compared to therapeutic ND in overall survival (RR 0.40, 95% CI 0.19 to 0.84; 67 participants) and disease‐free survival (HR 0.32, 95% CI 0.12 to 0.84; 67 participants). Four individual trials assessed locoregional recurrence, but could not be meta‐analysed; one trial favoured elective ND over therapeutic delayed ND, while the others were inconclusive.
Two trials compared elective radical ND with elective selective ND, but we were unable to pool the data for two outcomes. Neither study found evidence of a difference in overall survival or disease‐free survival. A single trial found no evidence of a difference in recurrence.
One trial compared surgery plus radiotherapy with radiotherapy alone, but data were unreliable because the trial stopped early and there were multiple protocol violations.
One trial comparing positron‐emission tomography‐computed tomography (PET‐CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (either before or after chemoradiotherapy), showed no evidence of a difference in mortality (HR 0.92, 95% CI 0.65 to 1.31; 564 participants). The trial did not provide usable data for the other outcomes.
Three single trials compared: surgery plus adjunctive radiotherapy versus chemoradiotherapy; supraomohyoid ND versus modified radical ND; and super selective ND versus selective ND. There were no useable data from these trials.
The reporting of adverse events was poor. Four trials measured adverse events. Only one of the trials reported quality of life as an outcome.
Authors' conclusions
Twelve randomised controlled trials evaluated ND surgery in people with oral cavity cancers; however, the evidence available for all comparisons and outcomes is very low certainty, therefore we cannot rely on the findings. The evidence is insufficient to draw conclusions about elective ND of clinically negative neck nodes at the time of removal of the primary tumour compared to therapeutic (delayed) ND. Two trials combined in meta‐analysis suggested there is no difference between these interventions, while one trial (which evaluated elective supraomohyoid ND) found that it may be associated with increased overall and disease‐free survival. One trial found elective ND reduced locoregional recurrence, while three were inconclusive. There is no evidence that radical ND increases overall or disease‐free survival compared to more conservative ND surgery, or that there is a difference in mortality between PET‐CT surveillance following chemoradiotherapy versus planned ND (before or after chemoradiotherapy). Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of people undergoing different surgical treatments.
A new species of Stolonivector (Lophocoleaceae) has been found from two separate sites in southern New Zealand. Stolonivector echioides has been assigned to this genus because it is has all the ...features of Stolonivector, namely the presence of stolons, a lack of secondary pigmentation, both lateral- and ventral-intercalary branching types, leafy branches that often become flagelliform, highly variable leaf apices on female shoots that are usually bifid towards the base of the stem becoming more shallowly bifid, retuse or entire towards the apex of the stem, and underleaves with apices that vary in the degree of division along the same stem ranging from undivided to deeply bifid. The most distinctive character that distinguishes this species from others in the genus is the spinose surface of leaves and perianths. This new addition brings the total number of New Zealand Stolonivector species to six, four of which are endemic.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Background
Caries is one of the most prevalent, preventable conditions worldwide. A wide variety of management options are available at different thresholds of disease, ranging from non‐operative ...preventive strategies such as improved oral hygiene, reduced sugar diet, and application of topical fluoride, to minimally invasive treatments for early lesions which are limited to enamel, through to selective removal and restoration for extensive lesions. The cornerstone of caries detection is a visual and tactile dental examination, however, an increasing array of methods of caries lesion detection have been proposed that could potentially support traditional methods of detection and diagnosis. Earlier identification of disease could afford patients the opportunity of less invasive treatment with less destruction of tooth tissue, reduce the need for treatment with aerosol‐generating procedures, and potentially result in a reduced cost of care to the patient and to healthcare services.
Objectives
Our primary objective was to determine the diagnostic accuracy of different electrical conductance devices for the detection and diagnosis of non‐cavitated coronal dental caries in different populations (children, adolescents, and adults) and when tested against different reference standards.
Search methods
Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 26 April 2019); Embase Ovid (1980 to 26 April 2019); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 26 April 2019); and the World Health Organization International Clinical Trials Registry Platform (to 26 April 2019). We studied reference lists as well as published systematic review articles.
Selection criteria
We included diagnostic accuracy studies that compared electrical conductance devices with a reference standard of histology or an enhanced visual examination. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. We included studies using previously extracted teeth or those that recruited participants with teeth believed to be sound or with early lesions limited to enamel.
Studies that explicitly recruited participants with more advanced lesions that were obviously into dentine or frankly cavitated were excluded.
Data collection and analysis
Two review authors extracted data independently using a piloted study data extraction form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2). Sensitivity and specificity with 95% confidence intervals (CIs) were reported for each study. This information was displayed as coupled forest plots, and plotted as summary receiver operating characteristic (SROC) plots, displaying the sensitivity‐specificity points for each study. Due to variability in thresholds we estimated diagnostic accuracy using hierarchical summary receiver operating characteristic (HSROC) methods.
Main results
We included seven studies reporting a total of 719 tooth sites or surfaces, with an overall prevalence of the target condition of 73% (528 tooth sites or surfaces). The included studies evaluated two index tests: the electronic caries monitor (ECM) (four studies, 475 tooth surfaces) and CarieScan Pro (three studies, 244 tooth surfaces). Six studies used histology as the reference standard, one used an enhanced visual examination. No study was considered to be at low risk of bias across all four domains or low concern for applicability or both. All studies were at high (five studies) or unclear (two studies) risk of bias for the patient selection domain. We judged two studies to be at unclear risk of bias for the index test domain, and one study to be at high risk of bias for the reference standard and flow and timing domains. We judged three studies to be at low concern for applicability for patient selection, and all seven studies to be of low concern for reference standard and flow and timing domains.
Studies were synthesised using a hierarchical method for meta‐analysis. There was variability in the results of the individual studies, with sensitivities which ranged from 0.55 to 0.98 and specificities from 0 to 1.00. These extreme values of specificity may be explained by a low number of healthy tooth surfaces in the included samples. The diagnostic odds ratio (DOR) was 15.65 (95% CI 1.43 to 171.15), and indicative of the variability in the included studies. Through meta‐regression we observed no meaningful difference in accuracy according to device type or dentition. Due to the small number of studies we were unable to formally investigate other potential sources of heterogeneity.
We judged the certainty of the evidence as very low, and downgraded for risk of bias due to limitations in the design and conduct of the included studies, imprecision arising from the relatively small number of surfaces studied, and inconsistency due to the variability of results.
Authors' conclusions
The design and conduct of studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ is particularly challenging. The evidence base to support the detection and diagnosis of caries with electrical conductance devices is sparse. Newer electrical conductance devices show promise and further research at the enamel caries threshold using a robust study design to minimise bias is warranted. In terms of applicability, any future studies should be carried out in a clinical setting to provide a realistic assessment within the oral cavity where plaque, staining, and restorations can be problematic.
Background
Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas ...oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.
Objectives
To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease‐free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.
Search methods
An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.
Selection criteria
We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.
Data collection and analysis
For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease‐free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment).
We contacted trial authors for additional information or clarification when necessary.
Main results
We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.
For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5‐fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate‐certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low‐certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low‐certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5‐fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low‐certainty evidence).
There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate‐certainty evidence). Among studies that compared post‐surgical adjuvant CRT, as compared to post‐surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate‐certainty evidence).
Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate‐certainty evidence).
Authors' conclusions
The results of this review demonstrate that chemotherapy in the curative‐intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:
To undertake a series of Cochrane Reviews to establish the diagnostic accuracy of index tests for ...the detection and diagnosis of dental caries. We propose a new review for each identified method for the detection and diagnosis of coronal caries in children and adults (five reviews in total); and one new review of the comparative accuracy of the identified methods, used alone or in combination.
Review 1. Visual or visual‐tactile examination according to detailed criteria.
Review 2. Radiography.
Review 3. Fluorescence.
Review 4. Electrical conductance.
Review 5. Fibre‐optic transillumination.
Review 6. Comparative accuracy review which will bring together the results of these reviews in a review of the comparative accuracy of the identified methods. Additional statistical analyses will be undertaken using the extracted data from all eligible studies that have evaluated one or more methods.
To undertake a series of Cochrane Reviews to establish the diagnostic accuracy of index tests for the detection and diagnosis of root dental caries, in adults. We propose the following new diagnostic test accuracy (DTA) review.
Review 7. Diagnostic tests for root caries in adults.
A single review for root caries will be completed due to a smaller volume of studies identified through a scoping search. The scoping search was completed during the grant application (January 2017) and interrogated MEDLINE only, in combination with existing systematic reviews of DTA for caries there is an anticipation that the visual, radiography and fluorescence reviews will each include over 100 studies (
Bader 2002
;
Bader 2004
;
Gimenez 2013
;
Gimenez 2015
;
Schwendicke 2015
).
Where sufficient studies are available, each individual review (numbers 1 to 5) will include evaluation of comparative accuracy of different index test methods/approaches, for example visual to evaluate differences between measurement indices i.e. ICDAS, Nyvad, ERK and other caries detection indices.
Aligned to the objectives listed above, the specific research questions answered through the suite of systematic reviews will include.
What is the diagnostic test accuracy of different tests for different purposes (detection or diagnosis), in different roles (adjunct to visual examination or independent test), in different populations (children: primary/mixed dentition, adolescents: immature permanent dentition, or adults: mature permanent dentition), and when tested against different reference standards.
What is the diagnostic test accuracy of each of the index tests compared to an appropriate reference standard for detecting and diagnosing initial stage decay on the occlusal and approximal tooth surfaces?
Do measures of sensitivity and specificity for single tests differ from the sensitivity and specificity of tests used in combination? Is there a benefit to using more than one index test as opposed to a single test?
What is the potential value of each index test at different positions in the clinical pathway? For example, 'disease‐free' individuals could be 'screened out' on the basis of a clinical examination, whilst those with a suspicion of disease would receive an x‐ray.
What is the comparative diagnostic test accuracy of the different index tests?
Background
The detection and diagnosis of caries at the earliest opportunity is fundamental to the preservation of tooth tissue and maintenance of oral health. Radiographs have traditionally been ...used to supplement the conventional visual‐tactile clinical examination. Accurate, timely detection and diagnosis of early signs of disease could afford patients the opportunity of less invasive treatment with less destruction of tooth tissue, reduce the need for treatment with aerosol‐generating procedures, and potentially result in a reduced cost of care to the patient and to healthcare services.
Objectives
To determine the diagnostic accuracy of different dental imaging methods to inform the detection and diagnosis of non‐cavitated enamel only coronal dental caries.
Search methods
Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles.
Selection criteria
We included diagnostic accuracy study designs that compared a dental imaging method with a reference standard (histology, excavation, enhanced visual examination), studies that evaluated the diagnostic accuracy of single index tests, and studies that directly compared two or more index tests. Studies reporting at both the patient or tooth surface level were included. In vitro and in vivo studies were eligible for inclusion. Studies that explicitly recruited participants with more advanced lesions that were obviously into dentine or frankly cavitated were excluded. We also excluded studies that artificially created carious lesions and those that used an index test during the excavation of dental caries to ascertain the optimum depth of excavation.
Data collection and analysis
Two review authors extracted data independently and in duplicate using a standardised data extraction form and quality assessment based on QUADAS‐2 specific to the clinical context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence regions. Comparative accuracy of different radiograph methods was conducted based on indirect and direct comparisons between methods. Potential sources of heterogeneity were pre‐specified and explored visually and more formally through meta‐regression.
Main results
We included 104 datasets from 77 studies reporting a total of 15,518 tooth sites or surfaces. The most frequently reported imaging methods were analogue radiographs (55 datasets from 51 studies) and digital radiographs (42 datasets from 40 studies) followed by cone beam computed tomography (CBCT) (7 datasets from 7 studies). Only 17 studies were of an in vivo study design, carried out in a clinical setting. No studies were considered to be at low risk of bias across all four domains but 16 studies were judged to have low concern for applicability across all domains. The patient selection domain had the largest number of studies judged to be at high risk of bias (43 studies); the index test, reference standard, and flow and timing domains were judged to be at high risk of bias in 30, 12, and 7 studies respectively.
Studies were synthesised using a hierarchical bivariate method for meta‐analysis. There was substantial variability in the results of the individual studies, with sensitivities that ranged from 0 to 0.96 and specificities from 0 to 1.00. For all imaging methods the estimated summary sensitivity and specificity point was 0.47 (95% confidence interval (CI) 0.40 to 0.53) and 0.88 (95% CI 0.84 to 0.92), respectively. In a cohort of 1000 tooth surfaces with a prevalence of enamel caries of 63%, this would result in 337 tooth surfaces being classified as disease free when enamel caries was truly present (false negatives), and 43 tooth surfaces being classified as diseased in the absence of enamel caries (false positives). Meta‐regression indicated that measures of accuracy differed according to the imaging method (Chi2(4) = 32.44, P < 0.001), with the highest sensitivity observed for CBCT, and the highest specificity observed for analogue radiographs. None of the specified potential sources of heterogeneity were able to explain the variability in results. No studies included restored teeth in their sample or reported the inclusion of sealants.
We rated the certainty of the evidence as low for sensitivity and specificity and downgraded two levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and the observed inconsistency of the results.
Authors' conclusions
The design and conduct of studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Low‐certainty evidence suggests that imaging for the detection or diagnosis of early caries may have poor sensitivity but acceptable specificity, resulting in a relatively high number of false‐negative results with the potential for early disease to progress. If left untreated, the opportunity to provide professional or self‐care practices to arrest or reverse early caries lesions will be missed. The specificity of lesion detection is however relatively high, and one could argue that initiation of non‐invasive management (such as the use of topical fluoride), is probably of low risk.
CBCT showed superior sensitivity to analogue or digital radiographs but has very limited applicability to the general dental practitioner. However, given the high‐radiation dose, and potential for caries‐like artefacts from existing restorations, its use cannot be justified in routine caries detection. Nonetheless, if early incidental carious lesions are detected in CBCT scans taken for other purposes, these should be reported. CBCT has the potential to be used as a reference standard in diagnostic studies of this type.
Despite the robust methodology applied in this comprehensive review, the results should be interpreted with some caution due to shortcomings in the design and execution of many of the included studies. Future research should evaluate the comparative accuracy of different methods, be undertaken in a clinical setting, and focus on minimising bias arising from the use of imperfect reference standards in clinical studies.
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