Office Of Health Assessment And Translation Research Articles

Effect of TiO2 Abutment Coatings on Peri-Implant Soft Tissue Behavior: A Systematic Review of In Vivo Studies.

Establishing a proper soft tissue adhesion around the implant abutment is essential to prevent microbial invasion, inhibit epithelial downgrowth, and obtain an optimal healing process. This systematic review aims to evaluate the real potential of TiO2 coating on the behavior of peri-implant soft tissue health and maintenance. A specific aim was to evaluate clinically and histologically the effect of TiO2 abutment coating on epithelial and connective tissue attachment. Electronic database searches were conducted from 1990 to 2023 in MEDLINE/PubMed and the Web of Science databases. In total, 15 out of 485 publications were included. Eight studies involved humans, and seven were animal studies. Exposure time ranges from 2 days to 5 years. The peri-implant soft tissue evaluations included clinical assessment (plaque index (PI), peri-implant probing pocket depth (PPD), and bleeding on probing (BoP)), histological as well as histomorphometric analysis. The Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies was used to evaluate the overall quality of the studies included in the review. The results showed some variation but remained within acceptable limits. Within the limitations of this systematic review, the present findings suggest that TiO2 coatings seem to influence soft tissue healing. TiO2-coated abutments with a roughness value between 0.2 and 0.5 μm enhance soft tissue health. Sol-gel-derived TiO2 coatings induced better soft tissue attachment than noncoated machined abutment surfaces. The anodized titanium abutments demonstrate comparable clinical and histological outcomes to conventional machined abutments. However, there was variation among the included studies concerning TiO2 coating characteristics and the measured outcomes used to evaluate the soft tissue response, and therefore, quantitative analysis was not feasible. Long-term in vivo studies with standardized soft tissue analysis and coating surface parameters are necessary before a definitive conclusion can be drawn. OSF Registration No.: 10.17605/OSF.IO/E5RQV.

Impact of organophosphate pesticides exposure on human semen parameters and testosterone: a systematic review and meta-analysis.

Organophosphate (OP) pesticides have been associated with a decline in semen quality, although there are still considerable arguments about the magnitude of the association. This study provides a systematic review and meta-analysis of the impacts of OP pesticides on semen quality and male reproductive hormones. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols. Strategic search was conducted using combined text words as search terms. The eligibility criteria were developed based on Population, Exposure, Comparator, Outcome, and Study designs (PECOS) framework. Relevant data were extracted, risk of bias was evaluated by The Office of Health Assessment and Translation (OHAT) tool, and certainty of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group guidelines. Quantitative meta-analysis was performed by using Review Manager. A total of 766 male subjects (349 exposed to OP pesticides and 417 unexposed controls) were included in the meta-analysis. There was no significant difference in the ejaculate volume, seminal fluid volume, sperm multiple anomaly index, sperm, and leukocytes levels of the OP-exposed subjects compared to the control. In addition, OP pesticides exposure did not significantly affect serum concentrations of FSH, LH, and testosterone in subjects who were exposed to OP pesticides compared to their unexposed counterparts. However, we found a significant reduction in the sperm count, sperm concentration, progressive sperm motility, total sperm motility, and normal sperm morphology of OP pesticides-exposed subjects compared to the unexposed subjects. However, after subtype and sensitivity analyses, exposure to OP pesticides did not reduce sperm count. Also, after sensitivity analysis, OP pesticides exposure did not alter progressive sperm motility. This study demonstrates that OP pesticides exposure reduced sperm count, concentration, total and progressive motility, and normal sperm morphology, possibly via a testosterone-independent mechanism.

The Role of Vitamins in Oral Potentially Malignant Disorders and Oral Cancer: A Systematic Review.

Micronutrients are vital for general and oral health, and their potential anti-cancer properties are documented. We explore beneficial vitamins for oral potentially malignant disorders (OPMDs) and oral cancer (OC), assessing the therapeutic impacts of essential vitamin supplementation. We systematically review evidence on vitamin supplementation's therapeutic effects for OPMDs and OC. Relevant studies were identified through comprehensive searches of MEDLINE, Evidence-Based Medicine, and Web of Science until 16 May 2023. All studies underwent risk of bias using criteria modified from the Office of Health Assessment and Translation (OHAT) tool. We analysed 80 papers. Vitamin K, studied in vitro, shows promising therapeutic potential. Vitamin C, investigated in vivo (animals and humans), demonstrated mixed animal results and generally positive human trial effects. Vitamin A's efficacy varied, with positive monotherapy or adjunct effects. Vitamins B and D showed therapeutic benefits. Oral cancer research was extensive, with a focus on oral lichen planus and oral leukoplakia among the 11 OPMDs. All bias levels were reported in 'selective reporting' and 'performance', except for "definitely high" in the 'selection', 'detection', and 'attrition/exclusion' domains. Evidence of vitamin interventions for OPMDs and OC ranges from mixed to promising. Standardizing the study design and outcomes would enhance future research.

Antimicrobial effect of platelet-rich fibrin: A systematic review of in vitro evidence-based studies.

This systematic review (SR) aimed to evaluate the antimicrobial potential of different types of platelet-rich fibrin (PRF) often used in regenerative treatments. An electronic search was performed in four databases and in Gray literature for articles published until January, 2023. The eligibility criteria comprised in vitro studies that evaluated the antimicrobial effect of different types of PRF. For the analysis of the risk of bias within studies, the modified OHAT (Office of Health Assessment and Translation) tool was used. For the evaluation of the results, a qualitative critical analysis was carried out in the synthesis of the results of the primary studies. Sixteen studies published between 2013 and 2021 were included in this SR. The antimicrobial effects of PRF variations (PRF, injectable PRF [I-PRF], PRF with silver nanoparticles [agNP-PRF], and horizontal PRF [H-PRF]), were analyzed against 16 types of bacteria from the oral, periodontal, and endodontic environments. All types of PRF showed significant antimicrobial action, with the antibacterial efficacy being more expressive than the fungal one. The I-PRF, H-PRF, and agNP-PRF subtypes improve antimicrobial activity. According to the OHAT analysis, no study was classified as having a high risk of bias. Evidence suggests that PRF variations have significant antimicrobial activity, with bacterial action being greater than fungal. Evolutions such as I-PRF, H-PRF, and agNP-PRF improve antimicrobial activity. Future studies analyzing the clinical effect of these platelets are fundamental. This SR was registered in INPLASY under number INPLASY202340016.

Effects of Radiofrequency Electromagnetic Field (RF-EMF) exposure on pregnancy and birth outcomes: A systematic review of experimental studies on non-human mammals

BackgroundThe World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency electromagnetic field (RF-EMF) exposure and adverse health effects. Within the project, 6 topics have been prioritized by an expert group, which include reproductive health outcomes. ObjectivesAccording to the protocol published in 2021, a systematic review and meta-analyses on the adverse effects of RF-EMF exposure during pregnancy in offspring of experimental animals were conducted. MethodsThree electronic databases (PubMed, Scopus and EMF Portal) were last searched on September 8 or 17, 2022. Based on predefined selection criteria, the obtained references were screened by two independent reviewers. Studies were included if they met the following criteria: 1) original, sham controlled experimental study on non-human mammals exposed in utero, published in peer-reviewed journals, 2) the experimental RF-EMF exposure was within the frequency range 100 kHz–300 GHz, 3) the effects of RF-EMF exposure on fecundity (litter size, embryonic/fetal losses), on the offspring health at birth (decrease of weight or length, congenital malformations, changes of sex ratio) or on delayed effects (neurocognitive alterations, female infertility or early-onset cancer) were studied. Study characteristics and outcome data were extracted by two reviewers. Risk of bias (RoB) was assessed using the Office of Health Assessment and Translation (OHAT) guidelines. Study results were pooled in a random effects meta-analysis comparing average exposure to no-exposure and in a dose–response meta-analysis using all exposure doses, after exclusion of studies that were rated at “high concern” for RoB. Subgroup analyses were conducted for species, Specific Absorption Rate (SAR) and temperature increase. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. ResultsEighty-eight papers could be included in this review. Effects on fecundity. The meta-analysis of studies on litter size, conducted at a whole-body average SAR of 4.92 W/kg, did not show an effect of RF-EMF exposure (MD 0.05; 95% CI −0.21 to 0.30). The meta-analysis of studies on resorbed and dead fetuses, conducted at a whole-body average SAR of 20.26 W/kg, showed a significant increase of the incidence in RF-EMF exposed animals (OR 1.84; 95% CI 1.27 to 2.66). The results were similar in the dose–response analysis. Effects on the offspring health at birth. The meta-analysis of studies on fetal weight, conducted at a whole-body average SAR of 9.83 W/kg, showed a small decrease in RF-EMF exposed animals (SMD 0.31; 95% CI 0.15 to 0.48). The meta-analysis of studies on fetal length, conducted at a whole-body average SAR of 4.55 W/kg, showed a moderate decrease in length at birth (SMD 0.45; 95% CI 0.07 to 0.83). The meta-analysis of studies on the percentage of fetuses with malformations, conducted at a whole-body average SAR of 6.75 W/kg, showed a moderate increase in RF-EMF exposed animals (SMD −0.45; 95% CI −0.68 to −0.23). The meta-analysis of studies on the incidence of litters with malformed fetuses, conducted at a whole-body average SAR of 16.63 W/kg, showed a statistically significant detrimental RF-EMF effect (OR 3.22; 95% CI 1.9 to 5.46). The results were similar in the dose–response analyses. Delayed effects on the offspring health. RF-EMF exposure was not associated with detrimental effects on brain weight (SMD 0.10; 95% CI −0.09 to 0.29) and on learning and memory functions (SMD −0.54; 95% CI −1.24 to 0.17). RF-EMF exposure was associated with a large detrimental effect on motor activity functions (SMD 0.79; 95% CI 0.21 to 1.38) and a moderate detrimental effect on motor and sensory functions (SMD −0.66; 95% CI −1.18 to −0.14). RF-EMF exposure was not associated with a decrease of the size of litters conceived by F2 female offspring (SMD 0.08; 95% CI −0.39 to 0.55). Notably, meta-analyses of neurobehavioural effects were based on few studies, which suffered of lack of independent replication deriving from only few laboratories. DiscussionThere was high certainty in the evidence for a lack of association of RF-EMF exposure with litter size. We attributed a moderate certainty to the evidence of a small detrimental effect on fetal weight. We also attributed a moderate certainty to the evidence of a lack of delayed effects on the offspring brain weight. For most of the other endpoints assessed by the meta-analyses, detrimental RF-EMF effects were shown, however the evidence was attributed a low or very low certainty. The body of evidence had limitations that did not allow an assessment of whether RF-EMF may affect pregnancy outcomes at exposure levels below those eliciting a well-known adverse heating impact.In conclusion, in utero RF-EMF exposure does not have a detrimental effect on fecundity and likely affects offspring health at birth, based on the meta-analysis of studies in experimental mammals on litter size and fetal weight, respectively. Regarding possible delayed effects of in utero exposure, RF-EMF probably does not affect offspring brain weight and may not decrease female offspring fertility; on the other hand, RF-EMF may have a detrimental impact on neurobehavioural functions, varying in magnitude for different endpoints, but these last findings are very uncertain.Further research is needed on the effects at birth and delayed effects with sample sizes adequate for detecting a small effect. Future studies should use standardized endpoints for testing prenatal developmental toxicity and developmental neurotoxicity (OECD TG 414 and 426), improve the description of the exposure system design and exposure conditions, conduct appropriate dosimetry characterization, blind endpoint analysis and include several exposure levels to better enable the assessment of a dose-response relationship. Protocol registration and publicationThe protocol was published in Pacchierotti et al., 2021 and registered in PROSPERO CRD42021227746 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227746).

Ambient temperature and mental health: a systematic review and meta-analysis

Increasing evidence indicates that ambient outdoor temperature could affect mental health, which is especially concerning in the context of climate change. We aimed to comprehensively analyse the current evidence regarding the associations between ambient temperature and mental health outcomes. We did a systematic review and meta-analysis of the evidence regarding associations between ambient outdoor temperature and changes in mental health outcomes. We searched WebOfScience, Embase, PsychINFO, and PubMed for articles published from database origin up to April 7, 2022. Eligible articles were epidemiological, observational studies in humans of all ages, which evaluated real-world responses to ambient outdoor temperature, and had mental health as a documented outcome; studies of manipulated or controlled temperature or those with only physical health outcomes were excluded. All eligible studies were synthesised qualitatively. If three or more studies reported the same or equivalent effect statistics and if they had equivalent exposure, outcome, and metrics, the studies were pooled in a random-effects meta-analysis. The risk of bias for individual studies was assessed using the Newcastle-Ottawa Scale. The quality of evidence across studies was assessed using the Office of Health Assessment and Translation (OHAT) approach. 114 studies were included in the systematic review, of which 19 were suitable for meta-analysis. Three meta-analyses were conducted for suicide outcomes: a 1°C increase in mean monthly temperature was associated with an increase in incidence of 1·5% (95% CI 0·8-2·2, p<0·001; n=1 563 109, seven effects pooled from three studies); a 1°C increase in mean daily temperature was associated with an increase in incidence of 1·7% (0·3-3·0, p=0·014; n=113 523, five effects pooled from five studies); and a 1°C increase in mean monthly temperature was associated with a risk ratio of 1·01 (95% CI 1·00-1·01, p<0·001; n=111 794, six effects pooled from three studies). Three meta-analyses were conducted for hospital attendance or admission for mental illness: heatwaves versus non-heatwave periods were associated with an increase in incidence of 9·7% (95% CI 7·6-11·9, p<0·001; n=362 086, three studies); the risk ratio at the 99th percentile of daily mean temperature compared with the 50th percentile was 1·02 (95% CI 1·01-1·03, p=0·006; n=532 296, three studies); and no significant association was found between a 10°C increase in daily mean temperature and hospital attendance. In a qualitative narrative synthesis, we found that ambient outdoor temperature (including absolute temperatures, temperature variability, and heatwaves) was positively associated with attempted and completed suicides (86 studies), hospital attendance or admission for mental illness (43 studies), and worse outcomes for community mental health and wellbeing (19 studies), but much of the evidence was of low certainty with high heterogeneity. Increased temperature and temperature variability could be associated with increased cases of suicide and suicidal behaviour, hospital attendance or admission for mental illness, and poor community health and wellbeing. Climate change is likely to increase temperature anomalies, variability, and heatwaves as well as average temperatures; as such, health system leaders and policy makers must be adequately prepared and should develop adaptation strategies. More high-quality, standardised research is required to improve our understanding of these effects. None.

Combining Photothermal Therapy with A NanohybridBased Drug Delivery Strategy for Slow-Released Doxorubicin: A Treatment for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. Surgical intervention remains the primary treatment option for resectable liver cancer. However, the low curative resection ratio, high metastatic ratio, and risk of recurrence make this treatment less than ideal. Additionally, the choice of liver transplantation is limited by the availability of donors. This literature review aimed to discuss the combination strategy of photothermal therapy and nanohybrid-based chemotherapy delivery, which are expected to address the challenges in HCC treatment. Methods: We conducted literature searches in Pubmed, Scopus, ProQuest, and Google Scholar using combined keywords such as “hepatocellular carcinoma”, “polyethylene glycol”, “doxorubicin”, “mesoporous silica”, “CuS”, “nanoparticle”, and “photothermal therapy”. Based on the assessment of validity and applicability aspects using modified Oxford CEBM (Center for Evidence-Based Management) and OHAT (Office of Health Assessment and Translation) checklist tools for preclinical studies, all the selected studies fulfilled the eligibility criteria. Results: Photothermal therapy promotes necrosis and apoptosis of HCC cells by ‘heating’ the cancer cells. Meanwhile, the chemotherapy agent doxorubicin, modified with mesoporous silica nanohybrids and encapsulated copper sulfate polyethylene glycol (PEG-DOX-MSN-CuS), enhances the efficiency and duration of drug circulation in the blood, reduces drug clearance, and minimizes retention by the reticuloendothelial system. By utilizing near-infrared light induction from photothermal therapy, doxorubicin can be slowly released, leading to significantly improved effectiveness. In vitro studies have demonstrated that this this combination strategy achieves over 90% HCC cell death at a chemotherapy concentration of 80 µg/mL, in conjunction with near-infrared light induction. The optimal release time for doxorubicin was recored at a concise 20 minutes. Conclusions: Given the numerous benefits associated with this combination of strategies, photothermal therapy using PEG-DOX-MSN-CuS holds significant expected to be a promising treatment for HCC.

Maternal pesticide exposure and risk of preterm birth: A systematic review and meta-analysis

BackgroundMaternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive. ObjectivesTo conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth. Data sourceFive English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023. Study eligibility criteria, participants, and interventionsTo be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth. Study appraisal, synthesis methods and confidence assessmentQuality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT. ResultsA total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = −0.10; 95%CI: −0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P < 0.05). For studies that collected samples at any time during pregnancy, pesticide exposure was found to be associated with shortened length of gestational age (β = −0.43; 95%CI: −0.81, −0.06). The confidence rating in the body of evidence was “moderate” and “very low” for preterm birth and gestational age at birth, respectively. ConclusionOur result suggested moderate evidence of an association between pesticide exposure and higher risk of preterm birth. Yet more studies are still needed with larger sample size and careful considerations of confounders and accuracy of outcome measurements. Attention is also required on other pesticide compounds in addition to organochlorine and organophosphorus pesticides, and on windows of susceptibility.

Extracellular Vesicle-Based Drug Delivery Systems for Head and Neck Squamous Cell Carcinoma: A Systematic Review.

It is estimated that there are over 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) worldwide each year, accounting for approximately 5% of all cancer cases. Current treatment options for HNSCC often cause significant side effects and functional impairments, thus there is a challenge to discover more acceptable treatment technologies. Extracellular vesicles (EVs) can be utilized for HNSCC treatment in several ways, for example, for drug delivery, immune modulation, as biomarkers for diagnostics, gene therapy, or tumor microenvironment modulation. This systematic review summarizes new knowledge regarding these options. Articles published up to 11 December 2022, were identified by searching the electronic databases PubMed/MEDLINE, Scopus, Web of Science, and Cochrane. Only full-text original research papers written in English were considered eligible for analysis. The quality of studies was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies, modified for the needs of this review. Of 436 identified records, 18 were eligible and included. It is important to note that the use of EVs as a treatment for HNSCC is still in the early stages of research, so we summarized information on challenges such as EV isolation, purification, and standardization of EV-based therapies in HNSCC.

The Plausible Use of Mango (Mangifera indica) Peel Isoquercitrin as Adjuvant Therapy for Colorectal Cancer: Translating Research from Bench to Bedside

A deadly and debilitating disease, colorectal cancer (CRC), is rapidly becoming a significant threat to public health. However, current therapeutic approaches are still hampered by various side effects. Due to its benefits and remarkable apoptotic impact on cancer cells, plant-derived flavonoids now garner interest as candidates for cancer therapy. Isoquercitrin, a flavonoid commonly found in fruit plants, especially mangoes, is notable due to its ability to inhibit cancer development through various mechanisms. This review aims to highlight the use of isoquercitrin extracted from mango peels in inhibiting CRC carcinogenesis. A literature search was done on Pubmed, Proquest, and Google Scholar using inclusion and exclusion criteria, and a narrative review was synthesised using the evidence gathered. Validity assessment was done through the the Office of Health Assessment and Translation (OHAT) and Oxford Center for Evidence-Based Medicine (CEBM) critical assessment tools. Evidence suggested that isoquercitrin is promising as adjuvant therapy in CRC. It may inhibit overaccumulation of cytoplasmic β-catenin and its translocation into the nucleus, thus downregulating the expression of target proto-oncogenes leading to carcinogenesis of colon crypts. Isoquercitrin concentration in mango peel is abundant, 557.7 mg/kg in dried mango peel and 31.0 mg/kg in pure extracts. A pharmacology study approved that a daily intake of 5.4 mg/kgBW of isoquercitrin has an effective anticancer effect. This substance has good oral bioavailability and is well-tolerated but inhibits the metabolising enzymes CYP1A1 and CYP1B1. In conclusion, isoquercitrin is a potential adjuvant in inhibiting CRC growth with minimum costs and side effects.

Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis

BackgroundThe health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. MethodsThe Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. ResultsThirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates—including smoking, body mass index, and individual and area-level socioeconomic status—and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter—pollutants with more than 10 studies—were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure–response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. ConclusionsThe overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high.

Association between exposure to light at night (LAN) and sleep problems: A systematic review and meta-analysis of observational studies.

Accumulating evidence have investigated the effects of nighttime light exposure on sleep problems. Nevertheless, the evidence of the relationship between light at night (LAN) and sleep problems remains scarce and inconsistent. Conducted a systematic review and meta-analysis based on observational studies to examine the association between LAN exposure and sleep problems among human subjects. We systematically searched three databases (PubMed, Web of Science, and Embase) to identify potentially eligible studies through May 25, 2022. The risk of bias and the quality of the generated evidence were assessed by two authors using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline. Random-effects model was applied to synthesize the risk estimates across eligible studies. The heterogeneity of included studies was quantified by the statistics of I2. A total of 7 cross-sectional studies comprising 577,932 participants were included. Individuals with higher levels of LAN exposure were associated with a 22 % (Summary Odds Ratio, SOR: 1.22, 95 %CI: 1.13-1.33) increased prevalence of sleep problems. The pooled effect size of indoor LAN exposure (SOR: 1.74, 95%CI: 1.27-2.37) associated with sleep problems was significantly higher than outdoor LAN exposure (SOR: 1.19, 95%CI: 1.11-1.29; P = 0.022). Additionally, dose-response analysis demonstrated that LAN intensity threshold exceeding 5.8 nW/cm2/sr (SOR: 1.04, 95%CI: 1.01-1.07) had a significant effect on sleep problems and the prevalence of sleep problems was increasing with increase in LAN intensity. Overall, our findings support the detrimental effects of LAN exposure on sleep. Maintaining bedroom darkness at night may be a feasible measure to reduce the prevalence of sleep problems. Future longitudinal studies with more advanced LAN assessment methods are required to move the field forward.

The cutaneous effects of blue light from electronic devices: a systematic review with health hazard identification.

The biologic effects of visible light, particularly blue light, on the skin at doses and irradiances representative of sunlight have been established. Recent research studies investigated the effects of blue light (BL) from electronic screen devices; however, it is unclear if the evidence can be generalized to real life. The aim of this systematic review was to evaluate available evidence regarding clinical effects of BL emitted from electronic devices on human skin using the framework established by the Office of Health Assessment and Translation (OHAT). A systematic literature search was conducted by two librarians in Ovid MEDLINE, Embase.com, and Web of Science for relevant articles published from 1946 to March 2022. In vitro and in vivo studies that investigated the effects of BL from electronic devices on skin were included. From the 87 articles gathered from database searches and 1 article identified from citation search, only 9 met the inclusion criteria (6 in vitro and 3 in vivo studies). Human and animal literature with the highest level of evidence ratings were considered with mechanistic data to form one of five human hazard identifications for each outcome category using the OHAT protocol: (1) known, (2) presumed, (3) suspected, (4) not classifiable, or (5) not identified to be a hazard to humans. Literature-based evidence integration did not identify exposure to BL from electronic devices as a hazard to skin pigmentation, redness, yellowness, or melasma exacerbation. Exposure to BL from electronic devices was not classified as a skin photoaging hazard. Low confidence in representative exposure characterization drove high OHAT risk-of-bias ratings for the majority of included studies. While these conclusions hold true for the limited existing data, a larger number of future studies with high-confidence evidence are needed to verify and strengthen hazard identification conclusions.

Data quality evaluation criteria for systematic review of epidemiology studies under the Toxic Substances Control Act (TSCA): refinement through practical application in risk evaluation

BACKGROUND AND AIM: The 2016 Frank R. Lautenberg Chemical Safety for the 21st Century Act and the 2017 Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (TSCA) require the U.S. Environmental Protection Agency (EPA) to conduct risk evaluations using the best available science and weight of the scientific evidence. Therefore, EPA has developed systematic review methods including data quality evaluation criteria to evaluate scientific studies in specific disciplines including epidemiology. EPA has aimed to refine these criteria for practical application in risk evaluation of high-priority chemicals under TSCA. METHODS: EPA considered the pros and cons of multiple existing systematic review frameworks and guidance documents and drew upon these methodologies to develop data quality evaluation domains, metrics, and criteria for the systematic review of epidemiology studies under TSCA. EPA refined these domains, metrics, and criteria through practical application to add specificity to increase consistency among evaluators and to harmonize with the evaluation of animal toxicology studies under TSCA. RESULTS: EPA adopted aspects of methods including the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) and EPA’s Integrated Risk Information System (IRIS) methods, but also aimed to be consistent with other disciplines and to address TSCA scientific standards. CONCLUSIONS: EPA has further refined data quality evaluation criteria for systematic review of epidemiology studies under TSCA in response to comments from peer reviewers, the public, the National Academies, and the TSCA Science Advisory Committee on Chemicals (SACC). Systematic review of epidemiology studies is a critical component of protecting human health under TSCA. DISCLAIMER: The views expressed in this presentation are solely those of the authors and do not represent the policies of EPA. Mention of trade names or commercial products should not be interpreted as an endorsement by EPA. KEY WORDS: Systematic Review, Data Quality Evaluation

Evidence synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution

Background: There is a long tradition in environmental health of using frameworks for evidence synthesis. Recently, frameworks were developed for evidence synthesis in clinical medicine, including Grading of Recommendations Assessment, Development and Evaluation (GRADE). The US Office of Health Assessment and Translation (OHAT) elaborated a GRADE type protocol for evidence synthesis in environmental health to assess the &amp;#x22;quality in a body of evidence”. Methods: We describe lessons learned in synthesizing evidence from observational studies of environmental health effects, drawing on our experience of applying the OHAT approach in a large systematic review on traffic-related air pollution and health outcomes. Results: We outlined key elements of and suggested improvements to the GRADE/OHAT approach. To maximize what can be learned from observational studies in environmental health, a &amp;#x22;narrative” approach is needed to complement the mechanistic up-and-downgrading of certain factors in the evaluation of the quality of a body of evidence. This &amp;#x22;narrative” approach links more directly to current and widely accepted evidence synthesis frameworks, such as from the US EPA and IARC. We argue that observational studies can offer high confidence evidence in environmental health, where randomized controlled trials are generally not feasible. All relevant studies should be included in evidence synthesis, beyond the subset of the available evidence often included in meta-analyses. Sources of heterogeneity can both strengthen and weaken the confidence in the evidence. Consistency of associations across study designs, populations, and exposure assessment methods provides additional confidence in the results. Publication bias should be explored beyond statistical methods and is not necessarily expected in large and collaborative studies. We call for identifying and quantifying possible key biases, their most likely direction, and their potential impacts on the results. Conclusions: GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them.

An Insight into the Role of Marine Biopolymer Alginate in Endodontics: A Review

Alginate is a natural marine biopolymer that has been widely used in biomedical applications, but research on its use as an endodontic material is still sparse in the literature. This pioneer review aims to summarize the emerging roles of alginate and to outline its prospective applications as a core biomaterial in endodontics. Ten electronic databases and five textbooks were used to perform a search of English-language literature on the use of alginate in endodontics published between January 1980 and June 2022. The risk of bias (RoB) of each included study was assessed using the Office of Health Assessment and Translation (OHAT) tool. Subsequently, studies were categorized into three tiers to represent the overall risk. Qualitative analysis was performed, and the articles were sorted into different thematic categories. An initial search yielded a total of 1491 articles, but only 13 articles were chosen. For most domains, all the studies were rated with ‘probably low’ or ‘definitely low’ RoB, except for domains 2 and 6. All included studies fall in the Tier 1 category and were either in vitro, in vivo, or ex vivo. Four thematic categories were identified: endodontic regeneration, intracanal medicament, filing material, and chelating agent. Based on the available evidence, alginate has emerged as a cell carrier and scaffold in regenerative endodontics, a microcapsule delivery system for intracanal medicaments, a chelating agent reinforcing material, and a root canal sealer. More well-designed experiments and clinical trials are needed to warrant the promising advent of this hydrogel-based biomaterial.

Systematic review of the physiological and health-related effects of radiofrequency electromagnetic field exposure from wireless communication devices on children and adolescents in experimental and epidemiological human studies.

BackgroundFor more than 20 years, the potential health risks of radiofrequency electromagnetic field (RF EMF) exposure from mobile communication devices on children and adolescents have been examined because they are considered sensitive population groups; however, it remains unclear whether such exposure poses any particular risk to them.ObjectivesThe aim of this review was to systematically analyze and evaluate the physiological and health-related effects of RF EMF exposures from wireless communication devices (mobile phones, cordless phones, Bluetooth, etc.) on children and adolescents.MethodsThis review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological limitations in individual studies were assessed using the Office of Health Assessment and Translation (OHAT) Risk-of-Bias Rating Tool for Human and Animal Studies.ResultsA total of 42 epidemiological and 11 experimental studies were eligible for this review. Most of the studies displayed several methodological weaknesses that limited the internal validity of the results. Due to a lack of consistency regarding the outcomes as well as the lack of scientific rigor in most reviewed studies, the body of evidence for the effects of RF EMF of mobile communication devices on subjective symptoms, cognition, and behavior in children and adolescents was low to inadequate. Evidence from the studies investigating early childhood development, brain activity, cancer, and physiological parameters was considered inadequate for drawing conclusions about possible effects.DiscussionOverall, the body of evidence allows no final conclusion on the question whether exposure to RF EMF from mobile communication devices poses a particular risk to children and adolescents. There has been rapid development in technologies generating RF EMF, which are extensively used by children and adolescents. Therefore, we strongly recommend high-quality systematic research on children and adolescents, since they are generally considered as sensitive age groups.

'SMART' implantable devices for spinal implants: a systematic review on current and future trends.

'SMART' implants refer to modified orthopedic implants that combine the biomechanical safety and efficacy of traditional devices with the intelligence of data-logging sensors. This review aims to systematically assess the available literature on SMART spinal implants and present these findings in a clinically relevant manner. A search of PubMed, Scopus, and Google Scholar databases was conducted by two separate reviewers. Information including sensor type, intended application, and sample size, was extracted from included studies. Risk of bias assessment was conducted using the Office of Health Assessment and Translation (OHAT) risk of bias tool. Eighteen studies were included for analysis. Eight studies involved SMART rods and ten studies used SMART vertebral body replacements (VBR). No more than 20 patients are reported to have received a SMART spinal implant. Including non-primary evidence, seven unique designs for SMART spinal implants were found. The majority of these used strain gauges with recent designs including thermometers and accelerometers. At present, SMART spinal implants have primarily focused on utilising strain gauges to report loading on the implant itself. This is a logical first step as it allows quantification of real-world requirements of an implant, detection of catastrophic failure, while also allowing researchers and clinicians to estimate changes in load sharing between newly forming bone and the implant itself, providing real-time information on the progression of healing and fusion. Future work includes documenting the correlation between data provided by these SMART implants and clinical findings, including complications such as pedicle screw loosening and interbody cage subsidence.

Effects of radiofrequency electromagnetic fields (RF EMF) on cancer in laboratory animal studies.

The carcinogenicity of radiofrequency electromagnetic fields (RF EMF) has been evaluated by the International Agency for Research on Cancer (IARC) in 2011. Based on limited evidence of carcinogenicity in humans and in animals, RF EMF were classified as possibly carcinogenic to humans (Group 2B). In 2018, based on a survey amongst RF experts, WHO prioritized six major topics of potential RF EMF related human health effects for systematic reviews. In the current manuscript, we present the protocol for the systematic review of experimental laboratory animal studies (cancer bioassays) on exposure to RF fields on the outcome of cancer in laboratory animals. In the framework of WHO's Radiation Program, the aim of this work is to systematically evaluate effects of RF EMF exposure on cancer in laboratory animals. WHO's Handbook (2014) for guideline development will be followed with appropriate adaptation. The selection of eligible studies will be based on Population, Exposures, Comparators, and Outcomes (PECO) criteria. We will include peer-reviewed articles and publicly available reports from government agencies reporting original data about animal cancer bioassays on exposure to RF EMF. The studies are identified by searching the following databases: MEDLINE (PubMed), Science Citation Index Expanded and Emerging Sources Citation Indes (Web of Science), Scopus, and the EMF Portal. No language or year-of-publication restrictions are applied. The methods and results of eligible studies will be presented in accordance with the PRISMA 2020 guidelines. Study evaluation of individual studies will be assessed using a risk of bias (RoB) tool developed by the Office of Health Assessment and Translation (OHAT) with appropriate considerations including sensitivity for evaluating RF EMF exposure in animal cancer bioassays. The final evaluation on the certainty of the evidence on a carcinogenic risk of RF EMF exposure in experimental animals will be performed using the OHAT Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach with appropriate considerations. The protocol has been registered in an open-source repository (PROSPERO). The study is partly financially supported by the World Health Organization. No additional funding was provided outside author salaries through their places of employment.

O04 A systematic review of the effect of therapeutic drug monitoring on patient health outcomes during treatment with penicillins

BackgroundDosing regimens guided by therapeutic drug monitoring (TDM) may be able to improve penicillin exposure in patients. Improved penicillin exposure could result in improved patient health outcomes. This systematic review aims to describe the impact TDM in penicillin treatment has on health outcomes, including the emergence of antimicrobial resistance (AMR).MethodsA search of four databases was conducted and supplemented with a hand search of the literature. Studies that measured concentrations of penicillins in patients, adjusted dosing regimens according to the result and reported health outcomes were selected. The risk of bias was assessed according to study type: randomized controlled trials (RCTs) were assessed with the revised Cochrane risk-of-bias tool for randomized trials (RoB2) assessment tool, the risk of bias in non-randomized studies (ROBINS-1) assessment tool was used to assess observational studies, and the Office of Health Assessment and Translation (OHAT) tool was used to assess case studies. The study characteristics were tabulated and described using a narrative synthesis.ResultsThree RCTs, 16 observational cohort studies and 9 case studies were included. None of the studies showed statistically significant improvements in health outcomes, when comparing groups receiving TDM and standard care. Five observational studies showed improvement in at least one health outcome statistically significantly associated with target attainment: mortality,1–5 bacterial persistence,1,4,5 ICU length of stay,4 treatment efficacy,1,4,6 and suppression of AMR.4 However there was a high risk of bias in all of these studies for health outcomes. Most had pharmacological primary outcomes and were underpowered to detect health outcomes. All three RCTs and four (25%) observational studies found that the use of penicillin TDM was associated with improved pharmacological target attainment. Only one study was found that assessed the impact of β-lactams TDM on AMR and found that target attainment of 100% ƒT>4×MIC was significantly associated with suppression of resistance. No studies found a detrimental effect of penicillin TDM on health outcomes. A meta-analysis was not performed due to the heterogeneity of the included studies.ConclusionsThere is little evidence to suggest that TDM improves health outcomes, however neither health outcomes nor reductions in emergence of AMR were adequately addressed by currently published studies. The evaluation of health outcomes was not the primary aim of the majority of the included studies, consequently those that did include these outcomes were underpowered to detect a difference. Observational studies often did not take into account co-interventions, or confounding factors, resulting in a high risk of bias. Large variations in how TDM of penicillins was implemented and the different populations used meant that a quantitative synthesis of results was not suitable. Recommendations to standardize penicillin TDM are a challenge currently, as there is no clear evidence of optimal conditions. Suitably powered studies designed to assess clinical outcomes are required to resolve the ambiguity surrounding the impacts of TDM on clinical outcomes, and to address the gap of the impacts on AMR. Further, appropriate standardized protocols and concentration targets for penicillin TDM in humans need to be identified for it to be implemented successfully.