Leveraging artificial intelligence to detect ethical concerns in medical research: a case study.

BACKGROUND: Institutional review boards (IRBs) have been criticised for delays in approvals for research proposals due to inadequate or inexperienced IRB staff. Artificial intelligence (AI), particularly large language models (LLMs), has significant potential to assist IRB members in a prompt and efficient reviewing process. METHODS: Four LLMs were evaluated on whether they could identify potential ethical issues in seven validated case studies. The LLMs were prompted with queries related to the proposed eligibility criteria of the study participants, vulnerability issues, information to be disclosed in the informed consent document (ICD), risk-benefit assessment and justification of the use of a placebo. Another query was issued to the LLMs to generate ICDs for these case scenarios. RESULTS: All four LLMs were able to provide answers to the queries related to all seven cases. In general, the responses were homogeneous with respect to most elements. LLMs performed suboptimally in identifying the suitability of the placebo arm, risk mitigation strategies and potential risks to study participants in certain case studies with a single prompt. However, multiple prompts led to better outputs in all of these domains. Each of the LLMs included all of the fundamental elements of the ICD for all case scenarios. Use of jargon, understatement of benefits and failure to state potential risks were the key observations in the AI-generated ICD. CONCLUSION: It is likely that LLMs can enhance the identification of potential ethical issues in clinical research, and they can be used as an adjunct tool to prescreen research proposals and enhance the efficiency of an IRB.

Nicotine replacement therapy and oral health: a network meta-analysis of adverse effects in randomized trials.

BACKGROUND: Nicotine replacement therapies (NRTs) are the primary pharmacological option for smokers looking to quit. However, they can lead to oral health issues, including aphthous ulcers, gastric irritation resulting in tooth wear, mouth irritation, soreness, and dryness, which may decrease patient adherence. Dentists should be integrated into the tobacco cessation team to prevent, detect, and manage these oral side effects associated with NRT use. Therefore, the objective of this network meta-analysis is to examine the relationship between different forms of NRTs and their oral side effects. METHODOLOGY: Databases were screened for literature and full text articles were obtained for eligible studies. Relevant data was extracted. NMA Studio was used to perform random-effects network meta-analysis to generate mixed treatment comparison pooled estimates from odds ratios (OR) and 95% confidence intervals (CI). The forest plot was generated, and the network diagram was drawn for key comparisons. The OR and 95% CI were estimated from the data on the number of patients that reported the oral side effects in the included studies. RESULTS: A total of 21 articles were included. The Risk of Bias assessment revealed a moderate to low risk across all domains for the included studies. The mixed treatment comparison pooled estimates indicated that nicotine gum was significantly associated with the occurrence of aphthous ulcers [2.25 (1.03, 4.90)] and gastric reflux/vomiting [4.40 (1.51, 12.80)]. Additionally, the results showed that nasal spray significantly caused mouth/throat irritation [5.37 (1.03, 27.92)] and taste disturbance [4.87 (2.83, 8.37)] in comparison to tested NRT interventions. CONCLUSION: Significant oral side effects are associated with NRT use, as demonstrated in this study. Dentists should implement tobacco cessation methods in their practices, including pharmacotherapy, to effectively monitor these patients. Continuous education and certification programs should be mandatory for dentists who want to practice tobacco cessation. This should also be included in the undergraduate dental curriculum to help dentists gain confidence in prescribing NRT. Standard evidence-based guidelines should be published to outline possible methods for encouraging tobacco cessation in dental settings.

Disinformation about COVID-19 Preventions and Treatments: Analysis of USFDA Warning Letters.

COVID-19 poses a challenge beyond the virus itself, in that lockdown has been associated increased use of the internet and social media. Disinformation about prevention and treatment strategies for COVID-19 can have lethal consequences. The United States Food and Drug Administration (USFDA) is currently monitoring the compliance of manufacturing firms as well as medicinal product advertisers to the Federal Food, Drug, and Cosmetic Act, 21 USC § 321(h) regulations. In the event of noncompliance in the form of advertising products without prior USFDA approval for specific indications, doses, or route of administration, warning letters (WLs) are issued. WLs are intended to address the concerns identified by USFDA and encourage the recipient to take corrective steps to avoid similar instances in the future. We analyzed 182 WLs that were issued for noncompliance with drugs/devices related to either treatment, prevention, or testing of COVID-19 infections. The medicinal product website was identified as the major source of disinformation, followed by disseminated information on Facebook, Twitter, and Instagram. Nearly four-fifths were related to drugs, followed by devices and biologicals. Several biologicals, as well as allopathic, herbal, and non-herbal drugs were identified in the WLs. We observed that noncompliance with the USFDA regulations in terms of advertising a variety of products for prevention and treatment of COVID-19 infection was widely prevalent. More efforts are required by the respective national drug regulatory authorities to initiate or continue their monitoring of disinformation that may have lethal consequences.

Oral side effects of locally delivered nicotine replacement therapy: A meta-analysis of randomized controlled trials.

BACKGROUND: Nicotine replacement therapy is the first choice pharmacotherapy for smoking cessation. Oral side effects caused due to NRT lead to discontinuation of treatment. The objective of this meta-analysis was to look for the certainty of evidence on the number of patients that reported oral side effects due to the use of NRT. METHOD: Eligible studies were selected and data extraction was carried out independently into a pre-tested data extraction form. Risk of bias was assessed using Cochrane Tool. The heterogeneity between the studies was assessed using Chi-square and I2 tests. Mean difference and Odds ratio at 95% confidence interval were the effect estimates. GRADE working group approach was used to assess the quality of evidence. RESULTS: Twenty-eight studies were included with moderate to low risk of bias. The pooled estimates revealed a statistically significant number of patients developed mouth or throat irritation (2.54 [1.23, 5.25]), or oral soreness (2.22 [1.40, 3.55]) or gastric reflux or vomiting (1.97 [1.34, 2.90]) due to NRT. CONCLUSION: It is important to understand that significant implications are caused due to NRT, on oral health. All patients on NRT must adhere to their regular dentist visits and must check their oral mucosa before initiating NRT.

Preprocedural mouth rinses for preventing transmission of infectious diseases through aerosols in dental healthcare providers.

BACKGROUND: Aerosols and spatter are generated in a dental clinic during aerosol-generating procedures (AGPs) that use high-speed hand pieces. Dental healthcare providers can be at increased risk of transmission of diseases such as tuberculosis, measles and severe acute respiratory syndrome (SARS) through droplets on mucosae, inhalation of aerosols or through fomites on mucosae, which harbour micro-organisms. There are ways to mitigate and contain spatter and aerosols that may, in turn, reduce any risk of disease transmission. In addition to personal protective equipment (PPE) and aerosol-reducing devices such as high-volume suction, it has been hypothesised that the use of mouth rinse by patients before dental procedures could reduce the microbial load of aerosols that are generated during dental AGPs. OBJECTIVES: To assess the effects of preprocedural mouth rinses used in dental clinics to minimise incidence of infection in dental healthcare providers and reduce or neutralise contamination in aerosols. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 February 2022. SELECTION CRITERIA: We included randomised controlled trials and excluded laboratory-based studies. Study participants were dental patients undergoing AGPs. Studies compared any preprocedural mouth rinse used to reduce contaminated aerosols versus placebo, no mouth rinse or another mouth rinse. Our primary outcome was incidence of infection of dental healthcare providers and secondary outcomes were reduction in the level of contamination of the dental operatory environment, cost, change in mouth microbiota, adverse events, and acceptability and feasibility of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from included studies, assessed the risk of bias in the studies and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data  MAIN RESULTS:  We included 17 studies with 830 participants aged 18 to 70 years. We judged three trials at high risk of bias, two at low risk and 12 at unclear risk of bias.  None of the studies measured our primary outcome of the incidence of infection in dental healthcare providers.  The primary outcome in the studies was reduction in the level of bacterial contamination measured in colony-forming units (CFUs) at distances of less than 2 m (intended to capture larger droplets) and 2 m or more (to capture droplet nuclei from aerosols arising from the participant's oral cavity). It is unclear what size of CFU reduction represents a clinically significant amount. There is low- to very low-certainty evidence that chlorhexidine (CHX) may reduce bacterial contamination, as measured by CFUs, compared with no rinsing or rinsing with water. There were similar results when comparing cetylpyridinium chloride (CPC) with no rinsing and when comparing CPC, essential oils/herbal mouthwashes or boric acid with water. There is very low-certainty evidence that tempered mouth rinses may provide a greater reduction in CFUs than cold mouth rinses. There is low-certainty evidence that CHX may reduce CFUs more than essential oils/herbal mouthwashes. The evidence for other head-to-head comparisons was limited and inconsistent.  The studies did not provide any information on costs, change in micro-organisms in the patient's mouth or adverse events such as temporary discolouration, altered taste, allergic reaction or hypersensitivity. The studies did not assess acceptability of the intervention to patients or feasibility of implementation for dentists.  AUTHORS' CONCLUSIONS: None of the included studies measured the incidence of infection among dental healthcare providers. The studies measured only reduction in level of bacterial contamination in aerosols. None of the studies evaluated viral or fungal contamination. We have only low to very low certainty for all findings. We are unable to draw conclusions regarding whether there is a role for preprocedural mouth rinses in reducing infection risk or the possible superiority of one preprocedural rinse over another. Studies are needed that measure the effect of rinses on infectious disease risk among dental healthcare providers and on contaminated aerosols at larger distances with standardised outcome measurement.

The variables associated with dental anxiety and their management in primary care dental clinics in Bahrain: a cross-sectional study.

BACKGROUND: 20-80% of adults presenting to a dental clinic experience anxiety. Negative past dental experiences and environmental factors such as the waiting area of a dental clinic or sound of a drill are commonly considered triggering factors for anxiety. Anxiety management strategies are considered a part of routine dental procedure, due to increased prevalence and compromised patient care. Hence the aim of the present study is to identify the prevalence and variables associated with dental anxiety and their management in patients visiting the primary care dental clinics in Bahrain. METHOD: Four hundred and eighty participants were included. A 3-part questionnaire deciphered the demographic characteristics of the participants, the dental procedure undertaken, the level of anxiety, and the management strategy used by the dentist. The pre and post-treatment MDAS scores were recorded. Paired t test, ANOVA and Wilcoxon signed rank test was used to test the level of significance between the variables and the mean MDAS scores. The p ≤ 0.05 was considered statistically significant. RESULTS: The prevalence of dental anxiety was 23.7% with moderate anxiety, and 11.4% with high anxiety. Females presented with a higher mean MDAS both pre and post-treatment compared with males. A statistically significant difference between the pre and post-treatment MDAS scores were observed in educated patients less than 50 years of age. Those with unpleasant previous dental experience showed statistically significant difference. Analyses of anxiety management techniques showed that single techniques worked better than combination techniques. Rest and breaks combined with any other technique of choice showed significant reduction in the MDAS scores post treatment. CONCLUSION: To conclude, all patients attending the dental clinic present with some level of anxiety that necessitates the dentist to use anxiety management strategies. Non-pharmacological methods that are non-invasive must be the first choice. Rests and breaks, with any technique of choice provides the best possible anxiety management. It is possible to achieve the desired anxiety reduction in single visit to complete the planned dental intervention, other than in patients who are dental phobic.

A network meta-analysis of CYP2C9, CYP2C9 with VKORC1 and CYP2C9 with VKORC1 and CYP4F2 genotype-based warfarin dosing strategies compared to traditional.

WHAT IS KNOWN AND OBJECTIVES: Variations in genotypes were observed in randomized clinical trials (RCTs) that evaluated genotype-based warfarin dosing. We carried out a network meta-analysis to assess whether any clinically significant differences exist between RCTs evaluating CYP2C9 with VKORC1, with CYP2C9 alone and CYP2C9, VKORC1, with CYP4F2 dosing strategies. METHODS: Electronic records were searched for RCTs comparing genotype-based warfarin with traditional-dosing strategies. Key outcomes included were the time to first therapeutic international normalized ratio (INR); time to stable INR or warfarin dose; percent time in therapeutic range (TTR); and the proportion of patients with supra-therapeutic INR. Weighted mean differences (WMD) and odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. RESULTS AND DISCUSSION: Twenty-six studies (7898 patients) were included. CYP2C9-based warfarin dosing was associated with a shorter time to first therapeutic INR (WMD: -2.73, 95% CI: -3.41, -2.05) and stable INR/warfarin dose (WMD: -8.1, 95% CI: -12.54, -3.66). CYP2C9 and VKORC1 were observed with a shorter time to first therapeutic INR (WMD: -1.92, 95% CI: -3.23, -0.61) and stable INR/warfarin dose (WMD: -4.6, 95% CI: -6.87, -2.34) along with a longer TTR (%) (WMD: 3.91, 95% CI: 1.18, 6.63). CYP2C9, VKORC1 and CYP4F2 were observed with a reduced proportion of patients with supra-therapeutic INR (OR: 0.68, 95% CI: 0.49, 0.93). Trial sequential analysis confirms the superior benefits of CYP2C9 with VKORC1 genotype. WHAT IS NEW AND CONCLUSION: The present evidence is supportive of personalizing warfarin dose based only on CYP2C9 and VKORC1 genotypes compared to traditional strategies. More RCTs are needed to delineate any benefit for adding CYP4F2 to provide sufficient power for pooled analysis. No convincing evidence exists supporting the role of CYP2C9 alone.

Topical corticosteroids for phimosis in children: a network meta-analysis of randomized clinical trials.

BACKGROUND: Corticosteroids and hyaluronidase are trialed for treating phimosis in children. We carried out the present network meta-analysis to compare the therapeutic effect of these drugs. METHODS: Electronic databases were searched for appropriate randomized clinical trials. Odds ratio (OR) with 95% confidence intervals (95% CI) was used as the effect estimate. A random-effects model was used for generating the pooled estimates. Rankogram plot was used for ranking the drugs. MAIN OUTCOME MEASURES: Proportions of patients with remission (partial/complete) and with complete remission. RESULTS: Mometasone (OR 6.53, 95% CI 2.85, 14.96), betamethasone/hyaluronidase (OR 12.1, 95% CI 4.27, 34.49), triamcinolone (OR 19.15, 95% CI 4.47, 81.96), dexamethasone (OR 21.38, 95% CI 5.71, 79.98), betamethasone (OR 23.02, 95% CI 6.92, 79.54), hydrocortisone (OR 23.2, 95% CI 5.91, 91.02) and methylprednisolone (OR 50.47, 95% CI 4.45, 572.72) were observed with significantly higher proportions of patients with remission (partial/complete) compared to placebo. Dexamethasone, triamcinolone, betamethasone, betamethasone/hyaluronidase, clobetasol, mometasone, and hydrocortisone were observed with significantly higher proportions of patients with complete remission compared to placebo. Beclomethasone was not observed to be superior to either placebo or other drugs. Rankogram plot revealed methylprednisolone followed by hydrocortisone had the maximum statistical probability of being 'the best' in the pool for remission and betamethasone followed by hydrocortisone for complete remission. CONCLUSION: Topical methylprednisolone, hydrocortisone, and betamethasone were observed with better clinical resolution of phimosis compared to other corticosteroids. Very high potent corticosteroids like beclomethasone and clobetasol were not observed with superior benefits compared to other corticosteroids. Considering low-potency, hydrocortisone shall be preferred until further evidence emerges.

Cerumenolytics with or without manual extraction for impacted earwax: A network meta-analysis of randomised clinical trials.

BACKGROUND: Many different substances for cerumenolysis have been evaluated in clinical trials. We carried out a systematic review and network meta-analysis to compare their effectiveness. METHODS: Electronic databases were searched for randomised clinical trials conducted in patients with impacted cerumen evaluating cerumenolytics. The primary outcome was the proportion of patients with wax clearance using manual techniques. Rankogram plot was used to assess the "best" cerumenolytic. Odds ratio (OR) with 95% confidence intervals (95% CI) was the effect estimate. RESULTS: Twenty-six studies were included in the systematic review and 25 in the meta-analysis. Sodium bicarbonate (OR: 2.68, 95% CI: 1.2, 6.1) and paradichlorobenzene (OR: 30.9, 95% CI: 5.9, 161.3) were associated with significantly greater proportions of patients with wax clearance following syringing compared to normal saline. Rankogram plot revealed paradichlorobenzene to have the highest probability of being the "best" cerumenolytic. Chlorobutanol was observed to be significantly better than normal saline in adults as well as following single application. Following multiple applications, glycerol, docusate sodium, hydrogen peroxide, oil, paradichlorobenzene, hydrogen peroxide/glycerol and arachis oil/chlorobutanol/paradichlorobenzene were observed with significant cerumenolytic activities. Urea/hydrogen peroxide/glycerol was observed with a significant cerumenolytic activity without the need for further interventions such as syringing/aspiration/suction. CONCLUSION: We observed several cerumenolytics to be effective in the treatment of impacted earwax when accompanied by additional manual techniques such as syringing/aspiration/suction.

Prevalence of periodontitis in obese patients in Bahrain: a cross-sectional study.

BACKGROUND: Adult obesity has been associated with various systemic diseases and is an increasing problem in Bahrain. Recent evidence indicates a correlation between adult obesity and periodontitis. Hence the aim of this study was to assess the prevalence of periodontitis in overweight/obese adults in Bahrain and to determine the factors associated with periodontitis in these obese adults. METHOD: This cross-sectional study was conducted in overweight subjects attending Ministry of Health (MOH) Nutrition Clinics at primary health centers in Bahrain. After obtaining the institutional ethics approval, the demographic and anthropometric data, including Body Mass Index (BMI) and waist circumference (WC) using World Health Organization (WHO) thresholds for severity of obesity, were recorded. Periodontal status was measured using the Community Periodontal Index (CPI) and the extent and severity of periodontal disease were categorized according to the number of sextants with CPI codes 3 and 4. RESULTS: A total of 372 participated with a mean age 44.0 (± 10.5) years for males, and 42.5 (± 11.2) years for females. Periodontitis was present in 361 (97%) of participants. Hypertension and diabetes were the most prevalent co-morbidities at 23.4% and 16% respectively. Mean WC was significantly greater in males at 114 cm (± 15.6) compared to females 109.5 cm (± 12.5) (p < 0.001). BMI was not associated with severity or extent of periodontitis but WC was weakly correlated in males but not in females (Spearman rho = + 0.2, p < 0.05). In the logistic regression model using overall WC to predict the severity of periodontitis, the adjusted OR was 1.02 (95% CI 1.00-1.04) and for age it was 1.05 (95% CI 1.00-1.07). CONCLUSION: The prevalence of periodontitis was high in this sample of overweight Bahrainis. BMI was not correlated with periodontitis but WC had a weak positive correlation. Implementation of periodontal health screening as a routine part of a nutrition clinic program is recommended.

Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.

BACKGROUND: Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. OBJECTIVES: To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. DATA COLLECTION AND ANALYSIS: Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. MAIN RESULTS: We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). AUTHORS' CONCLUSIONS: We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.

Fluoride varnish versus glutaraldehyde for hypersensitive teeth: a randomized controlled trial, meta-analysis and trial sequential analysis.

OBJECTIVE: Reports indicate Gluma and Duraphat are commonly used in-office agents to treat hypersensitive teeth. Considering this, the aim of this paper is to compare Gluma and Duraphat using a randomized controlled trial, meta-analysis collating evidences from previous studies and trial sequential analysis. MATERIALS AND METHODS: Thirty-eight participants were randomized. Hypersensitivity and visual analog scale (VAS) scores were recorded at baseline, 5 min and 7 days. Oral health-related quality of life (OHIP) questionnaire was administered at baseline and 7 days. Statistical analysis was performed to identify significant differences between the variables. For the meta-analysis, electronic data bases were searched and eligible data was extracted and analysed using RevMan 5.0. Trial sequential analysis was performed using O'Brien-Fleming boundary approach for the primary outcome. RESULTS: Both agents caused significant reduction in hypersensitivity and VAS score at 5 min and 7 days in the randomized trial with no superiority. The quality of life significantly improved in patients treated with both the agents. Four studies including the present trial in meta-analysis and trial sequential analysis indicated that Gluma produced significant reduction in VAS scores at 7 days. CONCLUSION: Gluma produces significant reduction in hypersensitivity at 7 days post treatment compared with Duraphat. There is definite lack of evidence on the long-term effect of these agents. CLINICAL RELEVANCE: This paper provides strong evidence on the use of Gluma for hypersensitive teeth. This also is a way forward to future research on long-term effects, adverse effects and cost-effectiveness studies.

Vasoactive Agents for Hepatorenal Syndrome: A Mixed Treatment Comparison Network Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials.

BACKGROUND: Hepatorenal syndrome (HRS) is a common complication among patients with cirrhosis, primarily attributable to vasodilation of renal vessels. Vasoactive agents are commonly used to treat HRS. The present network meta-analysis compares the vasoactive agents used in HRS. METHODS: We searched electronic databases for appropriate randomized controlled clinical trials in patients with HRS, comparing active interventions with either placebo or standard of care. The primary outcome was complete HRS reversal; secondary outcomes included partial HRS reversal, mortality, adverse events, and cardiovascular adverse events. The data were pooled using a random effects model. We also carried out direct comparisons for the primary outcome with trial sequential analysis. RESULTS: A total of 16 studies were included in the systematic review. Rates of complete HRS reversal were significantly higher with terlipressin and noradrenaline combined with albumin than with placebo (OR 6.65, 95% CI: 2.08-21.31 and 6.81, 95% CI: 1.87-24.83, respectively). No significant differences were observed in terms of mortality, partial HRS reversal, or adverse events for any of the interventions. However, cardiovascular adverse events were significantly higher with continuous-infusion terlipressin/albumin (OR 7.07, 95% CI: 1.23-40.62), bolus terlipressin/albumin (OR 7.39, 95% CI: 1.89, 28.94), octreotide/midodrine/albumin (OR 9.85, 95% CI: 1.1, 88.1), and noradrenaline/albumin (OR 15.24, 95% CI: 2.1, 112.6) than with albumin alone. Trial sequential analyses revealed adequate evidence to conclude that terlipressin combined with albumin was effective in achieving complete HRS reversal. DISCUSSION: Terlipressin combined with albumin shows strong evidence of improving short-term survival in patients with type 1 but not type 2 HRS. Through indirect comparison, noradrenaline with albumin was also associated with significant benefits in terms of HRS reversal.

Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials.

AIMS: Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. METHODS: Using an appropriate search strategy, randomized controlled trials on topical growth factors compared with standard of care in patients with DFU, were included. Proportion of patients with complete healing was the primary outcome. Odds ratio (95% confidence interval) was used as the effect estimate and random effects model was used for both direct and indirect comparisons. Markov Chain Monte Carlo simulation was used to obtain pooled estimates. Rankogram was generated based on surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 26 studies with 2088 participants and 1018 events were included. The pooled estimates for recombinant epidermal growth factor (rhEGF), autologous platelet rich plasma (PRP), recombinant human platelet-derived growth factor (rhPDGF) were 5.72 [3.34, 10.37], 2.65 [1.60, 4.54] and 1.97 [1.54, 2.55] respectively. SUCRA for rhEGF was 0.95. Sensitivity analyses did not reveal significant changes from the pooled estimates and rankogram. No differences were observed in the overall risk of adverse events between the growth factors. However, the growth factors were observed to lower the risk of lower limb amputation compared to standard of care. CONCLUSION: To conclude, rhEGF, rhPDGF and autologous PRP significantly improved the healing rate when used as adjuvants to standard of care, of which rhEGF may perform better than other growth factors. The strength of most of the outcomes assessed was low and the findings may not be applicable for DFU with infection or osteomyelitis. The findings of this study needs to be considered with caution as the results might change with findings from head-to-head studies.

Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis.

AIM: Several drugs have been used for treating non-alcoholic fatty liver disease (NAFLD). The present study is a network meta-analysis of such drugs. DESIGN, SETTING AND PATIENTS: Randomised clinical trials comparing drug interventions in patients with NAFLD were analysed. OR and weighted mean difference (95 % CI) were the effect estimates for categorical and numerical outcomes, respectively. Random-effects model was used to generate pooled estimates. Surface under the cumulative ranking curve was used to rank the treatments. MAIN OUTCOME MEASURES: Proportion of responders was the primary outcome measure and non-alcoholic steatohepatitis scores, liver enzymes, lipid profile, body mass index, homeostatic model assessment of insulin resistance, intrahepatic fat and adverse events were the key secondary outcomes. RESULTS: 116 studies were included in the systematic review and 106 in the meta-analysis. Elafibranor, gemfibrozil, metadoxine, obeticholic acid, pentoxifylline, pioglitazone, probiotics, telmisartan, vildagliptin and vitamin E significantly increased the response rate than standard of care. Various other drugs were observed to modify the secondary outcomes favourably. Probiotics was found with a better response in children; and elafibranor, obeticholic acid, pentoxifylline and pioglitazone in patients with type 2 diabetes mellitus. The quality of evidence observed was either low or very low. CONCLUSION: In patients with NAFLD, several drugs have been shown to have variable therapeutic benefit. However, the estimates and the inferences should be considered with extreme caution as it might change with the advent of future head-to-head clinical trials.

Efficacy of topical insulin in wound healing: A preliminary systematic review and meta-analysis of randomized controlled trials.

Topical insulin has been shown to promote wound healing in various studies. Considering the absence of a systematic review and quantitative synthesis on the same, the present study was carried out. Using an appropriate search strategy, electronic databases were searched for randomized controlled trials that have compared topical application of insulin in wounds with normal saline. Standardize mean differences were calculated for the following outcome measures: healing rate of ulcers/wound, percent granulation tissue growth, microvessel density, time to heal, wound area and ulcer severity score. Cochrane's risk of bias tool was used for each of the studies and RevMan 5.3 software was used to generate the pooled estimates and Forest plots. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group approach. A total of 8 studies were found eligible to be included in this review and 7 for the meta-analysis. The pooled estimates were as follows: healing rate-0.04 [-1.38, 1.46]; percent granulation tissue-10.99 [-10.07, 32.06], microvessel density-3.01 [-1.67, 7.69] and wound area--6.59 [-9.7, -3.48]. There was only one study for each of the following outcome measures: time to heal and ulcer severity score. Hence, pooling of the results was not attempted for these outcome measures. The studies conducted in this field were preliminary and it was difficult to draw any conclusion regarding the use of insulin topically for wound healing.

Nitrous Oxide and Midazolam Sedation: A Systematic Review and Meta-Analysis.

Nitrous oxide and midazolam have been used as sedative agents to decrease fear and anxiety associated with dental procedures. Although these agents have been widely used individually, the combination of the two is also commonly used. Four clinical trials were identified that compared the combination technique with the individual use of the drugs. The standardized mean difference (SMD) for each outcome measure was considered for final analysis. Three studies with 534 participants were included in the final meta-analysis, and the SMD [95% CI] was obtained as -0.15 [-0.32, 0.03] and was not statistically significant for cooperation scores. Two studies reported the dose of midazolam required for inducing sedation in 450 participants, and the pooled estimate of SMD [95% CI] was obtained as -0.29 [-0.48, -0.10] and was significant. Two studies with 450 participants reported the time taken to recover from sedation, and the pooled estimate of SMD [95% CI] was obtained as -0.20 [-0.39, -0.01] and favored the combination technique. To conclude, the combination technique combines the pros and cons of both drugs in causing fewer adverse effects due to midazolam by reducing the total dose and also helps to provide better acceptance of nitrous oxide inhalation.

A systematic review on the effectiveness of titratable over nontitratable mandibular advancement appliances for sleep apnea.

BACKGROUND: Mandibular advancement appliances are being tested for use in patients with obstructive sleep apnea (OSA). However, the effectiveness of titration of these appliances does not have conclusive evidence. Systematic reviews help us to compile all available clinical evidence using statistical principles. Hence, the aim of this systematic review is to identify the effectiveness of titratable over nontitratable mandibular advancement appliances in patients with mild to moderate OSA. This review objective is to identify if titration of these appliances produce significant benefits over fixed appliances. MATERIALS AND METHODOLOGY: Electronic databases were searched to identify eligible studies based on set inclusion criteria. Data extraction form was created and the data were extracted. The participants were mild to moderate OSA patients who received mandibular advancement appliances. Studies included a comparison between titratable and nontitratable mandibular advancement appliance. RESULTS: Of the five included studies, three were observational and two were a randomized trial. All these studies were conducted in adults. The outcome attributes were polysomnographic readings and apnea-hypopnea index (AHI). A significant heterogeneity was seen between the eligible studies and hence a meta-analysis could not be performed. CONCLUSION: The results from this systematic review did not show significant advantages of titratable appliances, although titratable appliances performed better from individual studies as regards to reduction in AHI and polysomnography. The reason is the lack of sufficient clinical trials on the same. More high quality randomized controlled trials comparing titratable and fixed appliances have to be initiated to get to conclusive evidence.

Therapeutic clowns in pediatrics: a systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Children and/or their parents are in fear and anxiety when admitted to hospitals or undergo invasive surgeries or investigations. Clown therapy has been shown as an effective measure in reducing this hospital fear and anxiety. Hence, we carried out a systematic compilation of the existing evidence on the clinical utility of hospital clowns in pediatric population. Electronic databases were searched with an appropriate search strategy, and only randomized controlled trials comparing the effect of clown therapy with standard care in children were included. The key outcome measures were as follows: extent of anxiety and pain felt by children and extent of state and trait parental anxiety. Random effect model was applied when moderate to severe heterogeneity was observed. Forest plot, I(2) statistics and risk of bias were evaluated using RevMan 5.3 software. A total of 19 studies were found eligible to be included in the systematic review and 16 for meta-analysis. The pooled SMD [95 % CI] for child anxiety score was -0.83 [-1.16, -0.51] favoring clown therapy. Similarly, a statistically significant reduction {SMD [95 % CI] -0.46 [-0.7, -0.21]} in the state anxiety was observed amongst parents. CONCLUSION: We found that hospital clowns play a significant role in reducing stress and anxiety levels in children admitted to hospitals as well as their parents. WHAT IS KNOWN: • Trials with clown doctors in pediatric population have shown conflicting results in allaying anxiety amongst children undergoing either hospitalization or invasive procedures What is new: • This is the first systematic review and meta-analysis on hospital clowns • We found out that hospital clowns reduce anxiety amongst children before undergoing either hospitalization or invasive procedures.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

INTRODUCTION: Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. METHOD: Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. RESULTS: A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. CONCLUSION: The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP.