Six-minute walk test as clinical end point in cardiomyopathy clinical trials, including ATTR-CM: a systematic literature review.

Aim: The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.

Musculoskeletal manifestations associated with transthyretin-mediated (ATTR) amyloidosis: a systematic review.

BACKGROUND: Hereditary and wild-type transthyretin-mediated (ATTRv and ATTRwt) amyloidoses result from the misfolding of transthyretin and aggregation of amyloid plaques in multiple organ systems. Diagnosis of ATTR amyloidosis is often delayed due to its heterogenous and non-specific presentation. This review investigates the association of musculoskeletal (MSK) manifestations with ATTR amyloidosis and the delay from the onset of these manifestations to the diagnosis of ATTR amyloidosis. METHODS: This systematic review utilized Medline and EMBASE databases. Search criteria were outlined using a pre-specified patient, intervention, comparator, outcome, time, study (PICOTS) criteria and included: amyloidosis, ATTR, and MSK manifestations. Publication quality was assessed utilizing Joanna Briggs Institute (JBI) critical appraisal checklists. The search initially identified 7,139 publications, 164 of which were included. PICOTS criteria led to the inclusion of epidemiology, clinical burden and practice, pathophysiology, and temporality of MSK manifestations associated with ATTR amyloidosis. 163 publications reported on ATTR amyloidosis and MSK manifestations, and 13 publications reported on the delay in ATTR amyloidosis diagnosis following the onset of MSK manifestations. RESULTS: The MSK manifestation most frequently associated with ATTR amyloidosis was carpal tunnel syndrome (CTS); spinal stenosis (SS) and osteoarthritis (OA), among others, were also identified. The exact prevalence of different MSK manifestations in patients with ATTR amyloidosis remains unclear, as a broad range of prevalence estimates were reported. Moreover, the reported prevalence of MSK manifestations showed no clear trend or distinction in association between ATTRv and ATTRwt amyloidosis. MSK manifestations precede the diagnosis of ATTR amyloidosis by years, and there was substantial variation in the reported delay to ATTR amyloidosis diagnosis. Reports do suggest a longer diagnostic delay in patients with ATTRv amyloidosis, with 2 to 12 years delay in ATTRv versus 1.3 to 1.9 years delay in ATTRwt amyloidosis. CONCLUSION: These findings suggest that orthopedic surgeons may play a role in the early diagnosis of and treatment referrals for ATTR amyloidosis. Detection of MSK manifestations may enable earlier diagnosis and administration of effective treatments before disease progression occurs.

Understanding the Barriers and Attitudes toward Influenza Vaccine Uptake in the Adult General Population: A Rapid Review.

Influenza is a common respiratory infection associated with a substantial clinical, humanistic, and economic burden globally. Vaccines are essential to prevent and control influenza and are recommended by public-health agencies, such as the WHO and US CDC; however, vaccination rates vary considerably across the globe. This review aimed to investigate the perceived barriers and attitudes to influenza vaccination in the global population, in order to identify strategies that may improve influenza vaccination coverage. A structured literature search was undertaken to identify studies that reported on patient-reported attitudes towards influenza vaccination, focused on the adult general population in 16 prespecified countries. Eighty studies were included in this review. Negative attitude towards healthcare were found to be the most agreed upon barrier to vaccine uptake (31.1% agreement). The most agreed promoter of influenza vaccination was trust in healthcare services (62.0% agreement). Approximately 50% of participants intended to receive the influenza vaccine in the following season. To improve influenza vaccination coverage, healthcare workers must strengthen the foundation of substantial trust in healthcare services and provide educational materials that improve influenza vaccination knowledge among the adult general population.

Surgical interventions for treating extracapsular hip fractures in older adults: a network meta-analysis.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising. The majority of extracapsular hip fractures are treated surgically. OBJECTIVES: To assess the relative effects (benefits and harms) of all surgical treatments used in the management of extracapsular hip fractures in older adults, using a network meta-analysis of randomised trials, and to generate a hierarchy of interventions according to their outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science and five other databases in July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different treatments for fragility extracapsular hip fractures in older adults. We included internal and external fixation, arthroplasties and non-operative treatment. We excluded studies of hip fractures with specific pathologies other than osteoporosis or resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author completed data extraction which was checked by a second review author. We collected data for three outcomes at different time points: mortality and health-related quality of life (HRQoL) - both reported within 4 months, at 12 months and after 24 months of surgery, and unplanned return to theatre (at end of study follow-up). We performed a network meta-analysis (NMA) with Stata software, using frequentist methods, and calculated the differences between treatments using risk ratios (RRs) and standardised mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). We also performed direct comparisons using the same codes. MAIN RESULTS: We included 184 studies (160 RCTs and 24 quasi-RCTs) with 26,073 participants with 26,086 extracapsular hip fractures in the review. The mean age in most studies ranged from 60 to 93 years, and 69% were women. After discussion with clinical experts, we selected nine nodes that represented the best balance between clinical plausibility and efficiency of the networks: fixed angle plate (dynamic and static), cephalomedullary nail (short and long), condylocephalic nail, external fixation, hemiarthroplasty, total hip arthroplasty (THA) and non-operative treatment. Seventy-three studies (with 11,126 participants) with data for at least two of these treatments contributed to the NMA. We selected the dynamic fixed angle plate as a reference treatment against which other treatments were compared. This was a common treatment in the networks, providing a clinically appropriate comparison.  We downgraded the certainty of the evidence for serious and very serious risks of bias, and because some of the estimates included the possibility of transitivity owing to the proportion of stable and unstable fractures between treatment comparisons. We also downgraded if we noted evidence of inconsistency in direct or indirect estimates from which the network estimate was derived. Most estimates included the possibility of benefits and harms, and we downgraded the evidence for these treatments for imprecision.  Overall, 20.2% of participants who received the reference treatment had died by 12 months after surgery. We noted no evidence of any differences in mortality at this time point between the treatments compared. Effect estimates of all treatments included plausible benefits as well as harms. Short cephalomedullary nails had the narrowest confidence interval (CI), with 7 fewer deaths (26 fewer to 15 more) per 1000 participants, compared to the reference treatment (risk ratio (RR) 0.97, 95% CI 0.87 to 1.07). THA had the widest CI, with 62 fewer deaths (177 fewer to 610 more) per 1000 participants, compared to the reference treatment (RR 0.69, 95% CI 0.12 to 4.03). The certainty of the evidence for all treatments was low to very low. Although we ranked the treatments, this ranking should be interpreted cautiously because of the imprecision in all the network estimates for these treatments. Overall, 4.3% of participants who received the reference treatment had unplanned return to theatre. Compared to this treatment, we found very low-certainty evidence that 58 more participants (14 to 137 more) per 1000 participants returned to theatre if they were treated with a static fixed angle plate (RR 2.48, 95% CI 1.36 to 4.50), and 91 more participants (37 to 182 more) per 1000 participants returned to theatre if treated with a condylocephalic nail (RR 3.33, 95% CI 1.95 to 5.68). We also found that these treatments were ranked as having the highest probability of unplanned return to theatre. In the remaining treatments, we noted no evidence of any differences in unplanned return to theatre, with effect estimates including benefits as well as harms. The certainty of the evidence for these other treatments ranged from low to very low. We did not use GRADE to assess the certainty of the evidence for early mortality, but our findings were similar to those for 12-month mortality, with no evidence of any differences in treatments when compared to dynamic fixed angle plate. Very few studies reported HRQoL and we were unable to build networks from these studies and perform network meta-analysis.  AUTHORS' CONCLUSIONS: Across the networks, we found that there was considerable variability in the ranking of each treatment such that there was no one outstanding, or subset of outstanding, superior treatments. However, static implants such as condylocephalic nails and static fixed angle plates did yield a higher risk of unplanned return to theatre. We had insufficient evidence to determine the effects of any treatments on HRQoL, and this review includes data for only two outcomes. More detailed pairwise comparisons of some of the included treatments are reported in other Cochrane Reviews in this series. Short cephalomedullary nails versus dynamic fixed angle plates contributed the most evidence to each network, and our findings indicate that there may be no difference between these treatments. These data included people with both stable and unstable extracapsular fractures. At this time, there are too few studies to draw any conclusions regarding the benefits or harms of arthroplasty or external fixation for extracapsular fracture in older adults. Future research could focus on the benefits and harms of arthroplasty interventions compared with internal fixation using a dynamic implant.

Surgical interventions for treating intracapsular hip fractures in older adults: a network meta-analysis.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a considerable challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising rapidly. The majority of intracapsular hip fractures are treated surgically. OBJECTIVES: To assess the relative effects (benefits and harms) of all surgical treatments used in the management of intracapsular hip fractures in older adults, using a network meta-analysis of randomised trials, and to generate a hierarchy of interventions according to their outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, and five other databases in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different treatments for fragility intracapsular hip fractures in older adults. We included total hip arthroplasties (THAs), hemiarthroplasties (HAs), internal fixation, and non-operative treatments. We excluded studies of people with hip fracture with specific pathologies other than osteoporosis or resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author completed data extraction which was checked by a second review author. We collected data for three outcomes at different time points: mortality and health-related quality of life (HRQoL) - both reported within 4 months, at 12 months, and after 24 months of surgery, and unplanned return to theatre (at end of study follow-up). We performed a network meta-analysis (NMA) with Stata software, using frequentist methods, and calculated the differences between treatments using risk ratios (RRs) and standardised mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). We also performed direct comparisons using the same codes. MAIN RESULTS: We included 119 studies (102 RCTS, 17 quasi-RCTs) with 17,653 participants with 17,669 intracapsular fractures in the review; 83% of fractures were displaced. The mean participant age ranged from 60 to 87 years and 73% were women.  After discussion with clinical experts, we selected 12 nodes that represented the best balance between clinical plausibility and efficiency of the networks: cemented modern unipolar HA, dynamic fixed angle plate, uncemented first-generation bipolar HA, uncemented modern bipolar HA, cemented modern bipolar HA, uncemented first-generation unipolar HA, uncemented modern unipolar HA, THA with single articulation, dual-mobility THA, pins, screws, and non-operative treatment. Seventy-five studies (with 11,855 participants) with data for at least two of these treatments contributed to the NMA. We selected cemented modern unipolar HA as a reference treatment against which other treatments were compared. This was a common treatment in the networks, providing a clinically appropriate comparison. In order to provide a concise summary of the results, we report only network estimates when there was evidence of difference between treatments. We downgraded the certainty of the evidence for serious and very serious risks of bias and when estimates included possible transitivity, particularly for internal fixation which included more undisplaced fractures. We also downgraded for incoherence, or inconsistency in indirect estimates, although this affected few estimates. Most estimates included the possibility of benefits and harms, and we downgraded the evidence for these treatments for imprecision.  We found that cemented modern unipolar HA, dynamic fixed angle plate and pins seemed to have the greatest likelihood of reducing mortality at 12 months. Overall, 23.5% of participants who received the reference treatment died within 12 months of surgery. Uncemented modern bipolar HA had higher mortality than the reference treatment (RR 1.37, 95% CI 1.02 to 1.85; derived only from indirect evidence; low-certainty evidence), and THA with single articulation also had higher mortality (network estimate RR 1.62, 95% CI 1.13 to 2.32; derived from direct evidence from 2 studies with 225 participants, and indirect evidence; very low-certainty evidence). In the remaining treatments, the certainty of the evidence ranged from low to very low, and we noted no evidence of any differences in mortality at 12 months.  We found that THA (single articulation), cemented modern bipolar HA and uncemented modern bipolar HA seemed to have the greatest likelihood of improving HRQoL at 12 months. This network was comparatively sparse compared to other outcomes and the certainty of the evidence of differences between treatments was very low. We noted no evidence of any differences in HRQoL at 12 months, although estimates were imprecise. We found that arthroplasty treatments seemed to have a greater likelihood of reducing unplanned return to theatre than internal fixation and non-operative treatment. We estimated that 4.3% of participants who received the reference treatment returned to theatre during the study follow-up. Compared to this treatment, we found low-certainty evidence that more participants returned to theatre if they were treated with a dynamic fixed angle plate (network estimate RR 4.63, 95% CI 2.94 to 7.30; from direct evidence from 1 study with 190 participants, and indirect evidence). We found very low-certainty evidence that more participants returned to theatre when treated with pins (RR 4.16, 95% CI 2.53 to 6.84; only from indirect evidence), screws (network estimate RR 5.04, 95% CI 3.25 to 7.82; from direct evidence from 2 studies with 278 participants, and indirect evidence), and non-operative treatment (RR 5.41, 95% CI 1.80 to 16.26; only from indirect evidence). There was very low-certainty evidence of a tendency for an increased risk of unplanned return to theatre for all of the arthroplasty treatments, and in particular for THA, compared with cemented modern unipolar HA, with little evidence to suggest the size of this difference varied strongly between the arthroplasty treatments. AUTHORS' CONCLUSIONS: There was considerable variability in the ranking of each treatment such that there was no one outstanding, or subset of outstanding, superior treatments. However, cemented modern arthroplasties tended to more often yield better outcomes than alternative treatments and may be a more successful approach than internal fixation. There is no evidence of a difference between THA (single articulation) and cemented modern unipolar HA in the outcomes measured in this review. THA may be an appropriate treatment for a subset of people with intracapsular fracture but we have not explored this further.

Arthroplasties for hip fracture in adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a huge challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising rapidly. The majority of hip fractures are treated surgically. This review evaluates evidence for types of arthroplasty: hemiarthroplasties (HAs), which replace part of the hip joint; and total hip arthroplasties (THAs), which replace all of it. OBJECTIVES: To determine the effects of different designs, articulations, and fixation techniques of arthroplasties for treating hip fractures in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, seven other databases and one trials register in July 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing different arthroplasties for treating fragility intracapsular hip fractures in older adults. We included THAs and HAs inserted with or without cement, and comparisons between different articulations, sizes, and types of prostheses. We excluded studies of people with specific pathologies other than osteoporosis and with hip fractures resulting from high-energy trauma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for seven outcomes: activities of daily living, functional status, health-related quality of life, mobility (all early: within four months of surgery), early mortality and at 12 months after surgery, delirium, and unplanned return to theatre at the end of follow-up. MAIN RESULTS: We included 58 studies (50 RCTs, 8 quasi-RCTs) with 10,654 participants with 10,662 fractures. All studies reported intracapsular fractures, except one study of extracapsular fractures. The mean age of participants in the studies ranged from 63 years to 87 years, and 71% were women. We report here the findings of three comparisons that represent the most substantial body of evidence in the review. Other comparisons were also reported, but with many fewer participants. All studies had unclear risks of bias in at least one domain and were at high risk of detection bias. We downgraded the certainty of many outcomes for imprecision, and for risks of bias where sensitivity analysis indicated that bias sometimes influenced the size or direction of the effect estimate. HA: cemented versus uncemented (17 studies, 3644 participants) There was moderate-certainty evidence of a benefit with cemented HA consistent with clinically small to large differences in health-related quality of life (HRQoL) (standardised mean difference (SMD) 0.20, 95% CI 0.07 to 0.34; 3 studies, 1122 participants), and reduction in the risk of mortality at 12 months (RR 0.86, 95% CI 0.78 to 0.96; 15 studies, 3727 participants). We found moderate-certainty evidence of little or no difference in performance of activities of daily living (ADL) (SMD -0.03, 95% CI -0.21 to 0.16; 4 studies, 1275 participants), and independent mobility (RR 1.04, 95% CI 0.95 to 1.14; 3 studies, 980 participants). We found low-certainty evidence of little or no difference in delirium (RR 1.06, 95% CI 0.55 to 2.06; 2 studies, 800 participants), early mortality (RR 0.95, 95% CI 0.80 to 1.13; 12 studies, 3136 participants) or unplanned return to theatre (RR 0.70, 95% CI 0.45 to 1.10; 6 studies, 2336 participants). For functional status, there was very low-certainty evidence showing no clinically important differences. The risks of most adverse events were similar. However, cemented HAs led to less periprosthetic fractures intraoperatively (RR 0.20, 95% CI 0.08 to 0.46; 7 studies, 1669 participants) and postoperatively (RR 0.29, 95% CI 0.14 to 0.57; 6 studies, 2819 participants), but had a higher risk of pulmonary embolus (RR 3.56, 95% CI 1.26 to 10.11, 6 studies, 2499 participants). Bipolar HA versus unipolar HA (13 studies, 1499 participants) We found low-certainty evidence of little or no difference between bipolar and unipolar HAs in early mortality (RR 0.94, 95% CI 0.54 to 1.64; 4 studies, 573 participants) and 12-month mortality (RR 1.17, 95% CI 0.89 to 1.53; 8 studies, 839 participants). We are unsure of the effect for delirium, HRQoL, and unplanned return to theatre, which all indicated little or no difference between articulation, because the certainty of the evidence was very low. No studies reported on early ADL, functional status and mobility. The overall risk of adverse events was similar. The absolute risk of dislocation was low (approximately 1.6%) and there was no evidence of any difference between treatments. THA versus HA (17 studies, 3232 participants) The difference in the risk of mortality at 12 months was consistent with clinically relevant benefits and harms (RR 1.00, 95% CI 0.83 to 1.22; 11 studies, 2667 participants; moderate-certainty evidence). There was no evidence of a difference in unplanned return to theatre, but this effect estimate includes clinically relevant benefits of THA (RR 0.63, 95% CI 0.37 to 1.07, favours THA; 10 studies, 2594 participants; low-certainty evidence). We found low-certainty evidence of little or no difference between THA and HA in delirium (RR 1.41, 95% CI 0.60 to 3.33; 2 studies, 357 participants), and mobility (MD -0.40, 95% CI -0.96 to 0.16, favours THA; 1 study, 83 participants). We are unsure of the effect for early functional status, ADL, HRQoL, and mortality, which indicated little or no difference between interventions, because the certainty of the evidence was very low.  The overall risks of adverse events were similar. There was an increased risk of dislocation with THA (RR 1.96, 95% CI 1.17 to 3.27; 12 studies, 2719 participants) and no evidence of a difference in deep infection. AUTHORS' CONCLUSIONS: For people undergoing HA for intracapsular hip fracture, it is likely that a cemented prosthesis will yield an improved global outcome, particularly in terms of HRQoL and mortality. There is no evidence to suggest a bipolar HA is superior to a unipolar prosthesis. Any benefit of THA compared with hemiarthroplasty is likely to be small and not clinically appreciable. We encourage researchers to focus on alternative implants in current clinical practice, such as dual-mobility bearings, for which there is limited available evidence.

Cephalomedullary nails versus extramedullary implants for extracapsular hip fractures in older adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a substantial challenge and burden to patients, healthcare systems and society. The increased proportion of older adults in the world population means that the absolute number of hip fractures is rising rapidly across the globe. Most hip fractures are treated surgically. This Cochrane Review evaluates evidence for implants used to treat extracapsular hip fractures. OBJECTIVES: To assess the relative effects of cephalomedullary nails versus extramedullary fixation implants for treating extracapsular hip fractures in older adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, the Cochrane Database of Systematic Reviews, Epistemonikos, ProQuest Dissertations & Theses, and the National Technical Information Service in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles, and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing cephalomedullary nails with extramedullary implants for treating fragility extracapsular hip fractures in older adults. We excluded studies in which all or most fractures were caused by a high-energy trauma or specific pathologies other than osteoporosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for seven critical outcomes: performance of activities of daily living (ADL), delirium, functional status, health-related quality of life, mobility, mortality (reported within four months of surgery as 'early mortality'; and reported from four months onwards, with priority given to data at 12 months, as '12 months since surgery'), and unplanned return to theatre for treating a complication resulting directly or indirectly from the primary procedure (such as deep infection or non-union). We assessed the certainty of the evidence for these outcomes using GRADE.  MAIN RESULTS: We included 76 studies (66 RCTs, 10 quasi-RCTs) with a total of 10,979 participants with 10,988 extracapsular hip fractures. The mean ages of participants in the studies ranged from 54 to 85 years; 72% were women. Seventeen studies included unstable trochanteric fractures; three included stable trochanteric fractures only; one included only subtrochanteric fractures; and other studies included a mix of fracture types. More than half of the studies were conducted before 2010. Owing to limitations in the quality of reporting, we could not easily judge whether care pathways in these older studies were comparable to current standards of care. We downgraded the certainty of the outcomes because of high or unclear risk of bias; imprecision (when data were available from insufficient numbers of participants or the confidence interval (CI) was wide); and inconsistency (when we noted substantial levels of statistical heterogeneity or differences between findings when outcomes were reported using other measurement tools). There is probably little or no difference between cephalomedullary nails and extramedullary implants in terms of mortality within four months of surgery (risk ratio (RR) 0.96, 95% CI 0.79 to 1.18; 30 studies, 4603 participants) and at 12 months (RR 0.99, 95% CI 0.90 to 1.08; 47 studies, 7618 participants); this evidence was assessed to be of moderate certainty. We found low-certainty evidence for differences in unplanned return to theatre but this was imprecise and included clinically relevant benefits and harms (RR 1.15, 95% CI 0.89 to 1.50; 50 studies, 8398 participants). The effect estimate for functional status at four months also included clinically relevant benefits and harms; this evidence was derived from only two small studies and was imprecise (standardised mean difference (SMD) 0.02, 95% CI -0.27 to 0.30; 188 participants; low-certainty evidence). Similarly, the estimate for delirium was imprecise (RR 1.22, 95% CI 0.67 to 2.22; 5 studies, 1310 participants; low-certainty evidence). Mobility at four months was reported using different measures (such as the number of people with independent mobility or scores on a mobility scale); findings were not consistent between these measures and we could not be certain of the evidence for this outcome. We were also uncertain of the findings for performance in ADL at four months; we did not pool the data from four studies because of substantial heterogeneity. We found no data for health-related quality of life at four months. Using a cephalomedullary nail in preference to an extramedullary device saves one superficial infection per 303 patients (RR 0.71, 95% CI 0.53 to 0.96; 35 studies, 5087 participants; moderate-certainty evidence) and leads to fewer non-unions (RR 0.55, 95% CI 0.32 to 0.96; 40 studies, 4959 participants; moderate-certainty evidence). However, the risk of intraoperative implant-related fractures was greater with cephalomedullary nails (RR 2.94, 95% CI 1.65 to 5.24; 35 studies, 4872 participants; moderate-certainty evidence), as was the risk of later fractures (RR 3.62, 95% CI 2.07 to 6.33; 46 studies, 7021 participants; moderate-certainty evidence). Cephalomedullary nails caused one additional implant-related fracture per 67 participants. We noted no evidence of a difference in other adverse events related or unrelated to the implant, fracture or both. Subgroup analyses provided no evidence of differences between the length of cephalomedullary nail used, the stability of the fracture, or between newer and older designs of cephalomedullary nail. AUTHORS' CONCLUSIONS: Extramedullary devices, most commonly the sliding hip screw, yield very similar functional outcomes to cephalomedullary devices in the management of extracapsular fragility hip fractures. There is a reduced risk of infection and non-union with cephalomedullary nails, however there is an increased risk of implant-related fracture that is not attenuated with newer designs. Few studies considered patient-relevant outcomes such as performance of activities of daily living, health-related quality of life, mobility, or delirium. This emphasises the need to include the core outcome set for hip fracture in future RCTs.

Clinical assessment for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy adults.

BACKGROUND: The early detection of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD), followed by appropriate treatment, may improve survival and reduce the risk for malignant transformation respectively. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To estimate the diagnostic test accuracy of conventional oral examination, vital rinsing, light-based detection, mouth self-examination, remote screening, and biomarkers, used singly or in combination, for the early detection of OPMD or OSCC in apparently healthy adults. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 October 2020), MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We conducted citation searches, and screened reference lists of included studies for additional references. SELECTION CRITERIA: We selected studies that reported the test accuracy of any of the aforementioned tests in detecting OPMD or OSCC during a screening procedure. Diagnosis of OPMD or OSCC was provided by specialist clinicians or pathologists, or alternatively through follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction, and quality assessment were carried out by at least two authors independently and in duplicate. Studies were assessed for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We reported the sensitivity and specificity of the included studies. We provided judgement of the certainty of the evidence using a GRADE assessment. MAIN RESULTS: We included 18 studies, recruiting 72,202 participants, published between 1986 and 2019. These studies evaluated the diagnostic test accuracy of conventional oral examination (10 studies, none new to this update), mouth self-examination (four studies, two new to this update), and remote screening (three studies, all new to this update). One randomised controlled trial of test accuracy directly evaluated conventional oral examination plus vital rinsing versus conventional oral examination alone. There were no eligible studies evaluating light-based detection or blood or salivary sample analysis (which tests for the presence of biomarkers for OPMD and OSCC). Only one study of conventional oral examination was judged as at overall low risk of bias and overall low concern regarding applicability. Given the clinical heterogeneity of the included studies in terms of the participants recruited, setting, prevalence of the target condition, the application of the index test and reference standard, and the flow and timing of the process, the data could not be pooled within the broader categories of index test. For conventional oral examination (10 studies, 25,568 participants), prevalence in the test accuracy sample ranged from 1% to 51%. For the seven studies with prevalence of 10% or lower, a prevalence more comparable to the general population, the sensitivity estimates were variable, and ranged from 0.50 (95% confidence interval (CI) 0.07 to 0.93) to 0.99 (95% CI 0.97 to 1.00); the specificity estimates were more consistent and ranged from 0.94 (95% CI 0.88 to 0.97) to 0.99 (95% CI 0.98 to 1.00). We judged the overall certainty of the evidence to be low, and downgraded for inconsistency and indirectness. Evidence for mouth self-examination and remote screening was more limited. We judged the overall certainty of the evidence for these index tests to be very low, and downgraded for imprecision, inconsistency, and indirectness. We judged the evidence for vital rinsing (toluidine blue) as an adjunct to conventional oral examination compared to conventional oral examination to be moderate, and downgraded for indirectness as the trial was undertaken in a high-risk population. AUTHORS' CONCLUSIONS: There is a lack of high-certainty evidence to support the use of screening programmes for oral cavity cancer and OPMD in the general population. Frontline screeners such as general dentists, dental hygienists, other allied professionals, and community healthcare workers should remain vigilant for signs of OPMD and OSCC.

Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions.

BACKGROUND: Squamous cell carcinoma is the most common form of malignancy of the oral cavity, and is often proceeded by oral potentially malignant disorders (OPMD). Early detection of oral cavity squamous cell carcinoma (oral cancer) can improve survival rates. The current diagnostic standard of surgical biopsy with histology is painful for patients and involves a delay in order to process the tissue and render a histological diagnosis; other diagnostic tests are available that are less invasive and some are able to provide immediate results. This is an update of a Cochrane Review first published in 2015. OBJECTIVES: Primary objective: to estimate the diagnostic accuracy of index tests for the detection of oral cancer and OPMD, in people presenting with clinically evident suspicious and innocuous lesions. SECONDARY OBJECTIVE: to estimate the relative accuracy of the different index tests. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were also searched for ongoing trials to 20 October 2020. No restrictions were placed on the language or date of publication when searching the electronic databases. We conducted citation searches, and screened reference lists of included studies for additional references. SELECTION CRITERIA: We selected studies that reported the diagnostic test accuracy of the following index tests when used as an adjunct to conventional oral examination in detecting OPMD or oral cavity squamous cell carcinoma: vital staining (a dye to stain oral mucosa tissues), oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis (which test for the presence of biomarkers in blood or saliva). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction and quality assessment were carried out by at least two authors, independently and in duplicate. Studies were assessed for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity. MAIN RESULTS: This update included 63 studies (79 datasets) published between 1980 and 2020 evaluating 7942 lesions for the quantitative meta-analysis. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (22 datasets), oral cytology (24 datasets), light-based detection or oral spectroscopy (24 datasets). Nine datasets assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis. Two studies were classed as being at low risk of bias across all domains, and 33 studies were at low concern for applicability across the three domains, where patient selection, the index test, and the reference standard used were generalisable across the population attending secondary care. The summary estimates obtained from the meta-analysis were: - vital staining: sensitivity 0.86 (95% confidence interval (CI) 0.79 to 0.90) specificity 0.68 (95% CI 0.58 to 0.77), 20 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; - oral cytology: sensitivity 0.90 (95% CI 0.82 to 0.94) specificity 0.94 (95% CI 0.88 to 0.97), 20 studies, sensitivity moderate-certainty evidence, specificity moderate-certainty evidence; - light-based: sensitivity 0.87 (95% CI 0.78 to 0.93) specificity 0.50 (95% CI 0.32 to 0.68), 23 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; and - combined tests: sensitivity 0.78 (95% CI 0.45 to 0.94) specificity 0.71 (95% CI 0.53 to 0.84), 9 studies, sensitivity very low-certainty evidence, specificity very low-certainty evidence. AUTHORS' CONCLUSIONS: At present none of the adjunctive tests can be recommended as a replacement for the currently used standard of a surgical biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for oral cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation. Potentially eligible studies of blood and salivary biomarkers were excluded from the review as they were of a case-control design and therefore ineligible. In the absence of substantial improvement in the tests evaluated in this updated review, further research into biomarkers may be warranted.

Visual or visual-tactile examination to detect and inform the diagnosis of enamel caries.

BACKGROUND: The detection and diagnosis of caries at the initial (non-cavitated) and moderate (enamel) levels of severity is fundamental to achieving and maintaining good oral health and prevention of oral diseases. An increasing array of methods of early caries 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: To determine the diagnostic accuracy of different visual classification systems for the detection and diagnosis of non-cavitated coronal dental caries for different purposes (detection and diagnosis) and in different populations (children or adults). SEARCH METHODS: Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 30 April 2020); Embase Ovid (1980 to 30 April 2020); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 30 April 2020); and the World Health Organization International Clinical Trials Registry Platform (to 30 April 2020). We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included diagnostic accuracy study designs that compared a visual classification system (index test) with a reference standard (histology, excavation, radiographs). This included cross-sectional 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 considered. Studies that explicitly recruited participants with caries into dentine or frank cavitation 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: We extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on QUADAS-2 specific to the review context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence intervals (CIs) and regions, and 95% prediction regions. The comparative accuracy of different classification systems was conducted based on indirect comparisons. Potential sources of heterogeneity were pre-specified and explored visually and more formally through meta-regression. MAIN RESULTS: We included 71 datasets from 67 studies (48 completed in vitro) reporting a total of 19,590 tooth sites/surfaces. The most frequently reported classification systems were the International Caries Detection and Assessment System (ICDAS) (36 studies) and Ekstrand-Ricketts-Kidd (ERK) (15 studies). In reporting the results, no distinction was made between detection and diagnosis. Only two studies were at low risk of bias across all four domains, and 15 studies were at low concern for applicability across all three domains. The patient selection domain had the highest proportion of high risk of bias studies (49 studies). Four studies were assessed at high risk of bias for the index test domain, nine for the reference standard domain, and seven for the flow and timing domain. Due to the high number of studies on extracted teeth concerns regarding applicability were high for the patient selection and index test domains (49 and 46 studies respectively). Studies were synthesised using a hierarchical bivariate method for meta-analysis. There was substantial variability in the results of the individual studies: sensitivities ranged from 0.16 to 1.00 and specificities from 0 to 1.00. For all visual classification systems the estimated summary sensitivity and specificity point was 0.86 (95% CI 0.80 to 0.90) and 0.77 (95% CI 0.72 to 0.82) respectively, diagnostic odds ratio (DOR) 20.38 (95% CI 14.33 to 28.98). In a cohort of 1000 tooth surfaces with 28% prevalence of enamel caries, this would result in 40 being classified as disease free when enamel caries was truly present (false negatives), and 163 being classified as diseased in the absence of enamel caries (false positives). The addition of test type to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi2(4) = 3.78, P = 0.44), nor did the addition of primary or permanent dentition (Chi2(2) = 0.90, P = 0.64). The variability of results could not be explained by tooth surface (occlusal or approximal), prevalence of dentinal caries in the sample, nor reference standard. Only one study intentionally included restored teeth in its sample and no studies reported the inclusion of sealants. We rated the certainty of the evidence as low, 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 inconsistency of results. AUTHORS' CONCLUSIONS: Whilst the confidence intervals for the summary points of the different visual classification systems indicated reasonable performance, they do not reflect the confidence that one can have in the accuracy of assessment using these systems due to the considerable unexplained heterogeneity evident across the studies. The prediction regions in which the sensitivity and specificity of a future study should lie are very broad, an important consideration when interpreting the results of this review. Should treatment be provided as a consequence of a false-positive result then this would be non-invasive, typically the application of fluoride varnish where it was not required, with low potential for an adverse event but healthcare resource and finance costs. 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. Studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Wherever possible future studies should be carried out in a clinical setting, to provide a realistic assessment of performance within the oral cavity with the challenges of plaque, tooth staining, and restorations, and consider methods to minimise bias arising from the use of imperfect reference standards in clinical studies.

Factors influencing dental trainees' choice of training programme and working patterns: a mixed-methods study.

Aims To assess the training programme and future career choices of newly qualified dental trainees.Methods Mixed-methods study combining a national questionnaire with focus groups administered to dental foundation trainees (DFTs) in England. Two regions chose not to participate; therefore, the questionnaire was sent to 588 DFTs and 226 (38.4%) responded. Forty-one DFTs participated in six regional focus groups.Results Location was the primary factor when choosing a training post, with 86% wanting to live and work near friends and family. Other influencers included affordability, availability of good training facilities and transport links, and proximity to their dental school. Focus group data found that perceived higher-quality training schemes were chosen over location in some circumstances. Most trainees wanted a career as an associate (67%) rather than a practice partner (32%) or owner (27%). Thirty-one percent aimed to practise on a private basis and 40% wanted to remain within the NHS. Women were significantly more likely than men to consider part-time working patterns (X2(2) = 9.761, p = 0.002). Part-time working was attractive as many found full-time clinical dentistry too stressful.Conclusions Geographical location is the key influencer on where dentists want to work and consideration needs to be given to interventions to address geographical disparities in graduate destinations. The strong desire to work part-time raises concerns about current workforce planning.

Internal fixation implants for intracapsular hip fractures in older adults.

BACKGROUND: Hip fractures are a major healthcare problem, presenting a huge challenge and burden to patients, healthcare systems and society. The increased proportion of older adults in the world population means that the absolute number of hip fractures is rising rapidly across the globe. The majority of hip fractures are treated surgically. This review evaluates evidence for types of internal fixation implants used in joint-preserving surgery for intracapsular hip fractures. OBJECTIVES: To determine the relative effects (benefits and harms) of different implants for the internal fixation of intracapsular hip fractures in older adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Web of Science, Cochrane Database of Systematic Reviews, Epistemonikos, Proquest Dissertations and Theses, and National Technical Information Service in July 2020. We also searched clinical trials databases, conference proceedings, reference lists of retrieved articles and conducted backward-citation searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing implants used for internal fixation of fragility intracapsular proximal femoral fractures in older adults. Types of implants were smooth pins (these include pins with fold-out hooks), screws, or fixed angle plates. We excluded studies in which all or most fractures were caused by specific pathologies other than osteoporosis or were the result of a high energy trauma. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. One review author extracted data and assessed risk of bias which was checked by a second review author. We collected data for seven outcomes: activities of daily living (ADL), delirium, functional status, health-related quality of life (HRQoL), mobility, mortality (reported within four months of surgery as early mortality, and at 12 months since surgery), and unplanned return to theatre for treating a complication resulting directly or indirectly from the primary procedure (such as deep infection or non-union). We assessed the certainty of the evidence for these outcomes using GRADE. MAIN RESULTS: We included 38 studies (32 RCTs, six quasi-RCTs) with 8585 participants with 8590 intracapsular fractures. The mean ages of participants in the studies ranged from 60 to 84 years; 73% were women, and 38% of fractures were undisplaced. We report here the findings of the four main comparisons, which were between different categories of implants. We downgraded the certainty of the outcomes for imprecision (when data were available from insufficient numbers of participants or the confidence interval (CI) was wide), study limitations (e.g. high or unclear risks of bias), and inconsistency (when we noted substantial levels of statistical heterogeneity). Smooth pins versus fixed angle plate (four studies, 1313 participants) We found very low-certainty evidence of little or no difference between the two implant types in independent mobility with no more than one walking stick (1 study, 112 participants), early mortality (1 study, 383 participants), mortality at 12 months (2 studies, 661 participants), and unplanned return to theatre (3 studies, 736 participants). No studies reported on ADL, delirium, functional status, or HRQoL. Screws versus fixed angle plates (11 studies, 2471 participants) We found low-certainty evidence of no clinically important differences between the two implant types in functional status using WOMAC (MD -3.18, 95% CI -6.35 to -0.01; 2 studies, 498 participants; range of scores from 0 to 96, lower values indicate better function), and HRQoL using EQ-5D (MD 0.03, 95% CI 0.00 to 0.06; 2 studies, 521 participants; range -0.654 (worst), 0 (dead), 1 (best)). We also found low-certainty evidence showing little or no difference between the two implant types in mortality at 12 months (RR 1.04, 95% CI 0.83 to 1.31; 7 studies, 1690 participants), and unplanned return to theatre (RR 1.10, 95% CI 0.95 to 1.26; 11 studies, 2321 participants). We found very low-certainty evidence of little or no difference between the two implant types in independent mobility (1 study, 70 participants), and early mortality (3 studies, 467 participants). No studies reported on ADL or delirium. Screws versus smooth pins (seven studies, 1119 participants) We found low-certainty evidence of no or little difference between the two implant types in mortality at 12 months (RR 1.07, 95% CI 0.85 to 1.35; 6 studies, 1005 participants; low-certainty evidence). We found very low-certainty evidence of little or no difference between the two implant types in early mortality (3 studies, 584 participants) and unplanned return to theatre (5 studies, 862 participants). No studies reported on ADL, delirium, functional status, HRQoL, or mobility. Screws or smooth pins versus fixed angle plates (15 studies, 3784 participants) In this comparison, we combined data from the first two comparison groups. We found low-certainty evidence of no or little difference between the two groups of implants in mortality at 12 months (RR 1.04, 95% CI.083 to 1.31; 7 studies, 1690 participants) and unplanned return to theatre (RR 1.02, 95% CI 0.88 to 1.18; 14 studies, 3057 participants). We found very low-certainty evidence of little or no difference between the two groups of implants in independent mobility (2 studies, 182 participants), and early mortality (4 studies, 850 participants). We found no additional evidence to support the findings for functional status or HRQoL as reported in 'Screws versus fixed angle plates'. No studies reported ADL or delirium. AUTHORS' CONCLUSIONS: There is low-certainty evidence that there may be little or no difference between screws and fixed angle plates in functional status, HRQoL, mortality at 12 months, or unplanned return to theatre; and between screws and pins in mortality at 12 months. The limited and very low-certainty evidence for the outcomes for which data were available for the smooth pins versus fixed angle plates comparison, as well as the other outcomes for which data were available for the screws and fixed angle plates, and screws and pins comparisons means we have very little confidence in the estimates of effect for these outcomes. Additional RCTs would increase the certainty of the evidence. We encourage such studies to report outcomes consistent with the core outcome set for hip fracture, including long-term quality of life indicators such as ADL and mobility.

Electrical conductance for the detection of dental caries.

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.

Imaging modalities to inform the detection and diagnosis of early caries.

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.

Transillumination and optical coherence tomography for the detection and diagnosis of enamel caries.

BACKGROUND: Caries is one of the most prevalent and preventable conditions worldwide. If identified early enough then non-invasive techniques can be applied, and therefore this review focusses on early caries involving the enamel surface of the tooth. The cornerstone of caries detection and diagnosis is a visual and tactile dental examination, although alternative approaches are available. These include illumination-based devices that could potentially support the dental examination. There are three categories of illumination devices that exploit various methods of application and interpretation, each primarily defined by different wavelengths, optical coherence tomography (OCT), near-infrared (NIR), and fibre-optic technology, which incorporates more recently developed digital fibre optics (FOTI/DIFOTI). OBJECTIVES: To estimate the diagnostic test accuracy of different illumination tests for the detection and diagnosis of enamel caries in children or adults. We also planned to explore the following potential sources of heterogeneity: in vitro or in vivo studies with different reference standards; tooth surface (occlusal, proximal, smooth surface, or adjacent to a restoration); single or multiple sites of assessment on a tooth surface; and the prevalence of caries into dentine. SEARCH METHODS: Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 15 February 2019); Embase Ovid (1980 to 15 February 2019); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 15 February 2019); and the World Health Organization International Clinical Trials Registry Platform (to 15 February 2019). We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included diagnostic accuracy study designs that compared the use of illumination-based devices with a reference standard (histology, enhanced visual examination with or without radiographs, or operative excavation). These included prospective studies that evaluated the diagnostic accuracy of a single index test and studies that directly compared two or more index tests. Both in vitro and in vivo studies of primary and permanent teeth were eligible for inclusion. We excluded studies that explicitly recruited participants with caries into dentine or frank cavitation. 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. The comparative accuracy of different illumination devices 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 24 datasets from 23 studies that evaluated 16,702 tooth surfaces. NIR was evaluated in 6 datasets (673 tooth surfaces), OCT in 10 datasets (1171 tooth surfaces), and FOTI/DIFOTI in 8 datasets (14,858 tooth surfaces). The participant selection domain had the largest number of studies judged at high risk of bias (16 studies). Conversely, for the index test, reference standard, and flow and timing domains the majority of studies were judged to be at low risk of bias (16, 12, and 16 studies respectively). Concerns regarding the applicability of the evidence were judged as high or unclear for all domains. Notably, 14 studies were judged to be of high concern for participant selection, due to selective participant recruitment, a lack of independent examiners, and the use of an in vitro study design. The summary estimate across all the included illumination devices was sensitivity 0.75 (95% confidence interval (CI) 0.62 to 0.85) and specificity 0.87 (95% CI 0.82 to 0.92), with a diagnostic odds ratio of 21.52 (95% CI 10.89 to 42.48). In a cohort of 1000 tooth surfaces with a prevalence of enamel caries of 57%, this would result in 142 tooth surfaces being classified as disease free when enamel caries was truly present (false negatives), and 56 tooth surfaces being classified as diseased in the absence of enamel caries (false positives). A formal comparison of the accuracy according to device type indicated a difference in sensitivity and/or specificity (Chi2(4) = 34.17, P < 0.01). Further analysis indicated a difference in the sensitivity of the different devices (Chi2(2) = 31.24, P < 0.01) with a higher sensitivity of 0.94 (95% CI 0.88 to 0.97) for OCT compared to NIR 0.58 (95% CI 0.46 to 0.68) and FOTI/DIFOTI 0.47 (95% CI 0.35 to 0.59), but no meaningful difference in specificity (Chi2(2) = 3.47, P = 0.18). In light of these results, we planned to formally assess potential sources of heterogeneity according to device type, but due to the limited number of studies for each device type we were unable to do so. For interpretation, we presented the coupled forest plots for each device type according to the potential source of heterogeneity. We rated the certainty of the evidence as low and downgraded two levels in total due to avoidable and unavoidable study limitations in the design and conduct of studies, indirectness arising from the in vitro studies, and imprecision of the estimates. AUTHORS' CONCLUSIONS: Of the devices evaluated, OCT appears to show the most potential, with superior sensitivity to NIR and fibre-optic devices. Its benefit lies as an add-on tool to support the conventional oral examination to confirm borderline cases in cases of clinical uncertainty. OCT is not currently available to the general dental practitioner, and so further research and development are necessary. FOTI and NIR are more readily available and easy to use; however, they show limitations in their ability to detect enamel caries but may be considered successful in the identification of sound teeth. Future studies should strive to avoid research waste by ensuring that recruitment is conducted in such a way as to minimise selection bias and that studies are clearly and comprehensively reported. In terms of applicability, any future studies should be undertaken in a clinical setting that is reflective of the complexities encountered in caries assessment within the oral cavity.

Fluorescence devices for the detection of dental caries.

BACKGROUND: Caries is one of the most prevalent and preventable conditions worldwide. If identified early enough then non-invasive techniques can be applied, and therefore this review focusses on early caries involving the enamel surface of the tooth. The cornerstone of caries detection is a visual and tactile dental examination, however alternative methods of detection are available, and these include fluorescence-based devices. There are three categories of fluorescence-based device each primarily defined by the different wavelengths they exploit; we have labelled these groups as red, blue, and green fluorescence. These devices could support the visual examination for the detection and diagnosis of caries at an early stage of decay. OBJECTIVES: Our primary objectives were to estimate the diagnostic test accuracy of fluorescence-based devices for the detection and diagnosis of enamel caries in children or adults. We planned to investigate the following potential sources of heterogeneity: tooth surface (occlusal, proximal, smooth surface or adjacent to a restoration); single point measurement devices versus imaging or surface assessment devices; and the prevalence of more severe disease in each study sample, at the level of caries into dentine. SEARCH METHODS: Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 30 May 2019); Embase Ovid (1980 to 30 May 2019); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 30 May 2019); and the World Health Organization International Clinical Trials Registry Platform (to 30 May 2019). We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included diagnostic accuracy study designs that compared a fluorescence-based device with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. Studies that explicitly recruited participants with caries into dentine or frank cavitation 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 has been displayed as coupled forest plots and summary receiver operating characteristic (SROC) plots, displaying the sensitivity-specificity points for each study. We estimated diagnostic accuracy using hierarchical summary receiver operating characteristic (HSROC) methods. We reported sensitivities at fixed values of specificity (median 0.78, upper quartile 0.90). MAIN RESULTS: We included a total of 133 studies, 55 did not report data in the 2 x 2 format and could not be included in the meta-analysis. 79 studies which provided 114 datasets and evaluated 21,283 tooth surfaces were included in the meta-analysis. There was a high risk of bias for the participant selection domain. The index test, reference standard, and flow and timing domains all showed a high proportion of studies to be at low risk of bias. Concerns regarding the applicability of the evidence were high or unclear for all domains, the highest proportion being seen in participant selection. Selective participant recruitment, poorly defined diagnostic thresholds, and in vitro studies being non-generalisable to the clinical scenario of a routine dental examination were the main reasons for these findings. The dominance of in vitro studies also means that the information on how the results of these devices are used to support diagnosis, as opposed to pure detection, was extremely limited. There was substantial variability in the results which could not be explained by the different devices or dentition or other sources of heterogeneity that we investigated. The diagnostic odds ratio (DOR) was 14.12 (95% CI 11.17 to 17.84). The estimated sensitivity, at a fixed median specificity of 0.78, was 0.70 (95% CI 0.64 to 0.75). In a hypothetical cohort of 1000 tooth sites or surfaces, with a prevalence of enamel caries of 57%, obtained from the included studies, the estimated sensitivity of 0.70 and specificity of 0.78 would result in 171 missed tooth sites or surfaces with enamel caries (false negatives) and 95 incorrectly classed as having early caries (false positives). We used meta-regression to compare the accuracy of the different devices for red fluorescence (84 datasets, 14,514 tooth sites), blue fluorescence (21 datasets, 3429 tooth sites), and green fluorescence (9 datasets, 3340 tooth sites) devices. Initially, we allowed threshold, shape, and accuracy to vary according to device type by including covariates in the model. Allowing consistency of shape, removal of the covariates for accuracy had only a negligible effect (Chi2 = 3.91, degrees of freedom (df) = 2, P = 0.14). Despite the relatively large volume of evidence we rated the certainty of the evidence as low, 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 high number of in vitro studies, and inconsistency due to the substantial variability of results. AUTHORS' CONCLUSIONS: There is considerable variation in the performance of these fluorescence-based devices that could not be explained by the different wavelengths of the devices assessed, participant, or study characteristics. Blue and green fluorescence-based devices appeared to outperform red fluorescence-based devices but this difference was not supported by the results of a formal statistical comparison. The evidence base was considerable, but we were only able to include 79 studies out of 133 in the meta-analysis as estimates of sensitivity or specificity values or both could not be extracted or derived. In terms of applicability, any future studies should be carried out in a clinical setting, where difficulties of caries assessment within the oral cavity include plaque, staining, and restorations. Other considerations include the potential of fluorescence devices to be used in combination with other technologies and comparative diagnostic accuracy studies.

ANTECEDENTES: La caries es una de las afecciones más frecuentes y prevenibles en todo el mundo. Si se identifican con suficiente antelación, se pueden aplicar técnicas no invasivas y, por lo tanto, esta revisión se centra en las caries tempranas que afectan la superficie del esmalte del diente. La piedra angular de la detección de la caries es una exploración dental visual y táctil; sin embargo, existen métodos alternativos de detección, entre los que se incluyen los dispositivos basados en la fluorescencia. Hay tres categorías de dispositivos basados en la fluorescencia, cada una de ellas definida principalmente por las diferentes longitudes de onda que utilizan; estos grupos se han llamado fluorescencia roja, azul y verde. Estos dispositivos podrían apoyar la exploración visual para la detección y el diagnóstico de la caries en una etapa temprana de descomposición. OBJETIVOS: Los objetivos principales fueron determinar la exactitud de la prueba diagnóstica de dispositivos basados en la fluorescencia para la detección y el diagnóstico de la caries del esmalte en niños o adultos. Se planificó investigar las siguientes fuentes potenciales de heterogeneidad: superficie dental (oclusal, proximal, superficie lisa o adyacente a una restauración); dispositivos de medición de punto único frente a dispositivos de imagen o de evaluación de superficie; y la prevalencia de enfermedades más graves en cada muestra de estudio, a nivel de caries en la dentina. MÉTODOS DE BÚSQUEDA: El documentalista del Grupo Cochrane de Salud Oral (Cochrane Oral Health Group) realizó una búsqueda en las siguientes bases de datos: MEDLINE Ovid (1946 al 30 de mayo de 2019); Embase Ovid (1980 al 30 de mayo de 2019); Registro de ensayos en curso de los Institutos Nacionales de Salud de los Estados Unidos (ClinicalTrials.gov, hasta el 30 de mayo de 2019); y la Plataforma de Registro Internacional de Ensayos Clínicos de la Organización Mundial de la Salud (hasta el 30 de mayo de 2019). Se estudiaron las listas de referencias y las revisiones sistemáticas publicadas. CRITERIOS DE SELECCIÓN: Se incluyeron diseños de estudios de exactitud diagnóstica que compararon un dispositivo basado en la fluorescencia con un estándar de referencia. Esto incluyó estudios prospectivos que evaluaron la exactitud diagnóstica de una única prueba índice y estudios que compararon directamente dos o más pruebas índice. Se excluyeron los estudios que reclutaron explícitamente a participantes con caries en la dentina o en la cavitación franca. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión extrajeron los datos de forma independiente mediante un formulario de extracción de datos de estudios piloto basado en la Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS­2). De cada estudio se informaron la sensibilidad y la especificidad con intervalos de confianza (IC) del 95%. Esta información se ha presentado en forma de diagramas de bosque (forest plot) emparejados y gráficos de curva resumen de rendimiento diagnóstico (SROC), que muestran los puntos de sensibilidad­especificidad de cada estudio. La exactitud diagnóstica se calculó mediante métodos de modelo jerárquico de curva resumen de rendimiento diagnóstico (HSROC). Se informaron sensibilidades a valores fijos de especificidad (mediana 0,78, cuartil superior 0,90). RESULTADOS PRINCIPALES: Se incluyeron un total de 133 estudios, 55 no informaron los datos en el formato 2 x 2 y no se pudieron incluir en el metanálisis. En el metanálisis se incluyeron 79 estudios que proporcionaron 114 conjuntos de datos y evaluaron 21 283 superficies dentales. Hubo alto riesgo de sesgo en el dominio de selección de los participantes. La prueba índice, el estándar de referencia y los dominios de flujo y tiempo mostraron que una alta proporción de los estudios tenían un bajo riesgo de sesgo. Las preocupaciones relacionadas con la aplicabilidad de la evidencia fueron altas o poco claras en todos los dominios, y la mayor proporción se observó en la selección de los participantes. El reclutamiento selectivo de los participantes, los umbrales diagnósticos mal definidos y el hecho de que los estudios in vitro no se puedan generalizar al escenario clínico de una exploración dental de rutina fueron las principales razones de estos hallazgos. El predominio de los estudios in vitro también hizo que la información sobre la forma en que se utilizan los resultados de esos dispositivos para apoyar el diagnóstico, en contraposición con la detección pura, fuera muy limitada. Hubo una variabilidad significativa en los resultados que no se pudo explicar por los diferentes dispositivos o dentición u otras fuentes de heterogeneidad que se investigaron. El odds ratio diagnóstico (ORD) fue 14,12 (IC del 95%: 11,17 a 17,84). La sensibilidad estimada, con una especificidad media fija de 0,78, fue 0,70 (IC del 95%: 0,64 a 0,75). En una cohorte hipotética de 1000 puntos o superficies dentales, con una prevalencia de caries del esmalte del 57%, obtenida de los estudios incluidos, la sensibilidad estimada de 0,70 y la especificidad de 0,78 daría lugar a 171 puntos o superficies dentales con caries del esmalte no detectados (falsos negativos) y 95 incorrectamente considerados con caries temprana (falsos positivos). Se utilizó la metarregresión para comparar la exactitud de los diferentes dispositivos para la fluorescencia roja (84 conjuntos de datos, 14 514 puntos dentales), la fluorescencia azul (21 conjuntos de datos, 3429 puntos dentales), y la fluorescencia verde (nueve conjuntos de datos, 3340 puntos dentales). Inicialmente, se permitió que el umbral, la forma y la exactitud variaran según el tipo de dispositivo, incluyendo covariables en el modelo. Permitiendo la homogeneidad de la forma, la eliminación de las covariables para la exactitud tuvo sólo un efecto insignificante (Ji2 = 3,91; grados de libertad [gl] = 2; p = 0,14). A pesar del volumen relativamente grande de evidencia, la certeza de las mismas se consideró baja, disminuyendo dos niveles en total, por el riesgo de sesgo debido a las limitaciones en el diseño y la realización de los estudios incluidos, los hallazgos indirectos derivados del elevado número de estudios in vitro y la incoherencia debida a la considerable variabilidad de los resultados. CONCLUSIONES DE LOS AUTORES: Existe una considerable variación en la ejecución de estos dispositivos basados en la fluorescencia que no se pudo explicar por las diferentes longitudes de onda de los dispositivos evaluados, los participantes ni las características de los estudios. Los dispositivos basados en la fluorescencia azul y verde parecieron superar a los basados en la fluorescencia roja, pero esta diferencia no estuvo respaldada por los resultados de una comparación estadística formal. La base de evidencia fue considerable, pero sólo fue posible incluir 79 estudios de 133 en el metanálisis, ya que no se pudieron extraer o derivar las estimaciones de los valores de sensibilidad o especificidad o ambos. En cuanto a la aplicabilidad, todo estudio futuro se debería realizar en un ámbito clínico, en el que las dificultades de la evaluación de la caries dentro de la cavidad oral incluyen la placa, la tinción y las restauraciones. Otras consideraciones son el potencial de los dispositivos de fluorescencia para ser utilizados en combinación con otras tecnologías y estudios comparativos de exactitud diagnóstica.

Tests to detect and inform the diagnosis of root caries.

BACKGROUND: Root caries is a well-recognised disease, with increasing prevalence as populations age and retain more of their natural teeth into later life. Like coronal caries, root caries can be associated with pain, discomfort, tooth loss, and contribute significantly to poorer oral health-related quality of life in the elderly. Supplementing the visual-tactile examination could prove beneficial in improving the accuracy of early detection and diagnosis. The detection of root caries lesions at an early stage in the disease continuum can inform diagnosis and lead to targeted preventive therapies and lesion arrest. OBJECTIVES: To assess the diagnostic test accuracy of index tests for the detection and diagnosis of root caries in adults, used alone or in combination with other tests. 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 one or more index tests (laser fluorescence, radiographs, visual examination, electronic caries monitor (ECM), transillumination), either independently or in combination, with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. In vitro and in vivo studies were eligible for inclusion but studies that artificially created carious lesions were excluded. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) specific to the review context. Estimates of diagnostic test accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each dataset. We planned to use hierarchical models for data synthesis and explore potential sources of heterogeneity through meta-regression. MAIN RESULTS: Four cross-sectional diagnostic test accuracy studies providing eight datasets with data from 4997 root surfaces were analysed. Two in vitro studies evaluated secondary root caries lesions on extracted teeth and two in vivo studies evaluated primary root caries lesions within the oral cavity. Four studies evaluated laser fluorescence and reported estimates of sensitivity ranging from 0.50 to 0.81 and specificity ranging from 0.40 to 0.80. Two studies evaluated radiographs and reported estimates of sensitivity ranging from 0.40 to 0.63 and specificity ranging from 0.31 to 0.80. One study evaluated visual examination and reported sensitivity of 0.75 (95% CI 0.48 to 0.93) and specificity of 0.38 (95% CI 0.14 to 0.68). One study evaluated the accuracy of radiograph and visual examination in combination and reported sensitivity of 0.81 (95% CI 0.54 to 0.96) and specificity of 0.54 (95% CI 0.25 to 0.81). Given the small number of studies and important differences in the clinical and methodological characteristics of the studies we were unable to pool the results. Consequently, we were unable to formally evaluate the comparative accuracy of the different tests considered in this review. Using QUADAS-2 we judged all four studies to be at overall high risk of bias, but only two to have applicability concerns (patient selection domain). Reasons included bias in the selection process, use of post hoc (data driven) positivity thresholds, use of an imperfect reference standard, and use of extracted teeth. We downgraded the certainty of the evidence due to study limitations and serious imprecision of the results (downgraded two levels), and judged the certainty of the evidence to be very low. AUTHORS' CONCLUSIONS: Visual-tactile examination is the mainstay of root caries detection and diagnosis; however, due to the paucity of the evidence base and the very low certainty of the evidence we were unable to determine the additional benefit of adjunctive diagnostic tests for the detection and diagnosis of root caries.

Do malocclusion and orthodontic treatment impact oral health? A systematic review and meta-analysis.

INTRODUCTION: Currently, there is limited evidence on the effects of malocclusion on oral health and whether the correction of malocclusion results in an improvement in oral health. In this review, we examined the evidence from randomized controlled trials and prospective cohort studies to provide information on any association between malocclusion and oral health and the effects of orthodontic treatment. METHODS: We conducted this review in 2 parts: (1) we looked at the impact of malocclusion on oral health, and (2) we reviewed the evidence on the effect of orthodontic treatment on oral health. We searched for randomized controlled trials and prospective cohort studies. The searches were completed for articles published between January 1, 1990 and October 8, 2018 and covered Medline via Ovid, Embase, and the Cochrane Database of Systematic Reviews. References of included articles and previous systematic reviews were hand-searched. No language restrictions were applied. Two members of the study team assessed the quality of the studies using the Appraisal Tool for Cross-Sectional Studies to appraise the quality of studies in part 1. The assessment was performed at the study level. Two authors assessed each study independently, with a third author consulted when a disagreement occurred. For studies in part 2, we used the Newcastle-Ottawa scale to assess the risk of bias. When studies were included in a Cochrane review, we incorporated the risk of bias assessment. We developed data extraction forms for each area of oral health under investigation (trauma, quality of life, caries, and periodontal disease). Each author piloted the form, and we held discussions to inform any necessary refinements. We extracted data from studies into 2 × 2 tables, which provided a binary analysis of malocclusion vs the outcome of interest. If these data were not available from the published paper, then studies were not included in the meta-analysis. The authors were contacted when possible to request data in this format. RESULTS: For part 1 of the study, we identified 87 studies. The overall quality was low. We could not include any of the data into an analysis because of a large variation in the nature of the studies, data collected, and outcome measures that were selected. For part 2 of the study, we found 7 studies; however, there were similar deficiencies in the data as in part 1, and thus, we could not reach any strong conclusions. CONCLUSIONS: Overall, there is an absence of published evidence regarding the effects of malocclusion on oral health and the impact of orthodontic treatment on oral health.

A comparison of dental fluorosis in adult populations with and without lifetime exposure to water fluoridation.

OBJECTIVES: There is a lack of evidence on the proportion and severity of fluorosis in adult populations exposed and not exposed to fluoridated water over their lifetimes. The aim of this study was to compare the proportion and severity of fluorosis in adults with lifetime exposure to water fluoridation with a nonexposed sample. A secondary aim was to report the gradient of fluorosis severity by age. METHODS: A cross-sectional study recruited a sample with lifetime exposure to water fluoridation and a matched, nonexposed group. 580 participants, aged 18-52 years (mean 34.3, SD 9.4) and 64% female, were recruited in general dental practices located in fluoridated (Birmingham and County Durham) and nonfluoridated areas (Manchester). Three digital images were taken of their incisors and an experienced examiner who was blind to exposure status viewed the images remotely and allocated fluorosis scores using the Thylstrup and Fejerskov (TF) scale. RESULTS: At TF ≥ 1 (any fluorosis), a significantly higher proportion of participants from the fluoridated area had fluorosis (F 39% NF 21.3%, P < 0.001), at the threshold TF ≥ 3 ("aesthetic concern"), the difference was no longer statistically significant (F 4.1%, NF 2.2%, P = 0.25). There was a gradient by age, whereby fluorosis was highest in the youngest and lowest in the oldest age group. CONCLUSIONS: Although fluorosis is more common in adults with lifetime exposure to water fluoridation than those with no exposure, the aesthetic impact of fluorosis seems to diminish with age.