Systematic review of the effectiveness and cost-effectiveness of Healozone for the treatment of occlusal pit/fissure caries and root caries.

Objectives: To assess the effectiveness and cost-effectiveness of HealOzone® (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a ‘patient kit’, which consists of toothpaste, oral rinse and oral spray all containing fluoride. Data sources: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). Review methods: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. Results: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies’ findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (£40.49 versus £24.78), but cost less for non-cavitated root caries (£14.63 versus £21.45). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator (£22.65 versus £33.39). Conclusions: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses

Systematic review of the effectiveness and cost-effectiveness of HealOzone® for the treatment of occlusal pit/fissure caries and root caries

Objectives: To assess the effectiveness and cost-effectiveness of HealOzone® (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a ‘patient kit’, which consists of toothpaste, oral rinse and oral spray all containing fluoride. Data sources: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). Review methods: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. Results: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies’ findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (£40.49 versus £24.78), but cost less for non-cavitated root caries (£14.63 versus £21.45). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator (£22.65 versus £33.39). Conclusions: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses

Low-dose vitamin D3 supplementation does not affect natural regulatory T cell population but attenuates seasonal changes in T cell-produced IFN-γ: Results from the D-SIRe2 randomised controlled trial

Background: Seasonal variations have been reported for immune markers. However, the relative contributions of sunlight and vitamin D variability on such seasonal changes are unknown. Objective: This double-blind, randomized, placebo-controlled trial tested whether daily 400 IU vitamin D3 supplementation affected short-term (12 weeks) and long-term (43 weeks) natural regulatory T cell (nTreg) populations in healthy participants. Design: 62 subjects were randomized equally to vitamin D versus placebo in March and assessed at baseline, April (4w), June (12w), September (25w) and January (43w). Circulating nTregs, ex vivo proliferation, IL-10 and IFN-γ productions were measured. Vitamin D metabolites and sunlight exposure were also assessed. Results: Mean serum 25-hydroxyvitamin D (25(OH)D) increased from 35.8(SD 3.0) to 65.3(2.6) nmol/L in April and remained above 70 nmol/L with vitamin D supplementation, whereas it increased from 36.4(3.2) to 49.8(3.5) nmol/L in June to fall back to 39.6(3.5) nmol/L in January with placebo. Immune markers varied similarly between groups according to the season, but independently of 25(OH)D. For nTregs, the mean (%CD3+CD4+CD127lo cells (SEM)) nadir observed in March (2.9(0.1)%) peaked in September at 4.0(0.2)%. Mean T cell proliferation peaked in June (33156(1813) CPM) returning to the nadir in January (17965 (978) CPM), while IL-10 peaked in June and reached its nadir in September (median (IQR) of 262(283) to (121(194) pg/ml, respectively). Vitamin D attenuated the seasonal increase in IFN-γ by ~28% with mean ng/ml (SEM) for placebo vs vitamin D, respectively, for April 12.5(1.4) vs 10.0(1.2) (p=0.02); June 13.9(1.3) vs 10.2(1.7) (p=0.02) and January 7.4(1.1) vs 6.0(1.1) (p=0.04). Conclusions: Daily low dose Vitamin D intake did not affect the nTregs population. There were seasonal variation in nTregs, proliferative response and cytokines, suggesting that environmental changes influence immune response, but the mechanism seems independent of vitamin D status. Vitamin D attenuated the seasonal change in T cell-produced IFN-γ, suggesting a decrease in effector response which could be associated with inflammation. Clinical trial identifier: ISRCTN 73114576 (https://www.isrctn.com

Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms:a systematic review conducted to inform new NICE DG30 diagnostic guidance

__Background:__ This study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met. __Methods:__ We conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model. __Results:__ Nine studies are included in this review. One additional study, included in our systematic review, was provided as 'academic in confidence' and cannot be described herein. When FIT was based on a single faecal sample and a cut-off of 10 μg Hb/g faeces, sensitivity estimates indicated that a negative result using either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC; the summary estimate of sensitivity for the OC-Sensor was 92.1%, based on four studies, and the only study of HM-JACKarc to assess the 10 μg Hb/g faeces cut-off reported a sensitivity of 100%. The corresponding specificity estimates were 85.8% (95% CI 78.3-91.0%) and 76.6%, respectively. When the diagnostic criterion was changed to include lower grades of neoplasia, i.e. the target condition included higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT assays was reduced. __Conclusions:__ There is evidence to suggest that triage using FIT at a cut-off around 10 μg Hb/g faeces has the potential to correctly rule out CRC and avoid colonoscopy in 75-80% of symptomatic patients. Systematic review registration: PROSPERO 4201603772

Genomic and molecular analyses identify molecular subtypes of pancreatic cancer recurrence

Pancreatic cancer (PC) remains a highly lethal malignancy, and most patients with localized disease that undergo surgical resection still succumb to recurrent disease. Pattern of recurrence after pancreatectomy is heterogenous, with some studies illustrating that site of recurrence can be associated with prognosis.1 Another study suggested that tumors that develop local and distant recurrence can be regarded as a homogenous disease with similar outcomes.2 Here we investigate novel molecular determinants of recurrence pattern after pancreatectomy for PC

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.Peer reviewe

National identity predicts public health support during a global pandemic (vol 13, 517, 2022) : National identity predicts public health support during a global pandemic (Nature Communications, (2022), 13, 1, (517), 10.1038/s41467-021-27668-9)

Publisher Copyright: © The Author(s) 2022.In this article the author name ‘Agustin Ibanez’ was incorrectly written as ‘Augustin Ibanez’. The original article has been corrected.Peer reviewe