The impact of HIV preexposure prophylaxis on bacterial sexually transmitted infection occurrence in MSM: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of preexposure prophylaxis (PrEP) initiation on bacterial sexually transmitted infection (STI) occurrence (overall; chlamydia; gonorrhea; syphilis), in MSM. DESIGN: Systematic review and meta-analysis. METHODS: Systematic searches were performed in PubMed, Embase, and Scopus without language restrictions until 1 February 2023. We sought studies reporting data for the estimation of incidence rate ratios (IRR), prevalence ratios or cumulative incidence ratios (the latter in equal time periods before and after PrEP initiation) regarding bacterial STI occurrence. Separate analyses were performed overall for any STI, syphilis, chlamydia and gonorrhea (overall; rectal; urethral; pharyngeal for the two latter conditions); ratios greater than unity denoted increase in STI occurrence after PrEP initiation. RESULTS: Twenty-three eligible studies with 11 776 participants (age range: 18-71 years) with a median follow-up of 12 months were included. Overall, PrEP initiation was associated with a significant increase in the occurrence of any STI (pooled effect size: 1.15, 95% confidence interval (CI): 1.04-1.26), any gonorrhea (pooled effect size: 1.17, 95% CI: 1.02-1.34), any chlamydia (pooled effect size: 1.31, 95% CI: 1.09-1.58) and rectal chlamydia (pooled effect size: 1.31, 95% CI: 1.05-1.64), whereas a borderline increase was found in urethral chlamydia (pooled effect size: 1.25, 95% CI: 0.99-1.60, P  = 0.064). Changes in pharyngeal chlamydia and site-specific gonorrhea occurrence did not reach statistical significance. Syphilis showed virtually no change after PrEP initiation (pooled effect size: 0.99, 95% CI: 0.72-1.37). CONCLUSION: These results highlight the need for more comprehensive, accessible STI testing to tackle bacterial STI infections in PrEP users.

Fixed versus Unfixed Combination of Topical Latanoprost/Timolol for Glaucoma: An Observational Study Investigating the Level of Adherence and Ocular Surface Health.

PURPOSE: To investigate the effect of fixed combination versus concomitant unfixed topical glaucoma treatment on patients' adherence and ocular surface health. PATIENTS AND METHODS: This is a 6-month, prospective, parallel-group, observational study in patients with ocular hypertension (OHT), primary open-angle glaucoma (POAG), or exfoliation glaucoma (XFG). A total of 142 patients with similar baseline characteristics were enrolled in this study. Seventy-one patients received a Latanoprost 0.005%/Timolol 0.5% fixed combination in the evening, whereas seventy-one patients received the unfixed treatment with Latanoprost 0.005% in the evening and Timolol 0.5% twice daily. The primary outcome was the adherence rate at baseline, and at the 3- and 6-month follow-up visits. The secondary outcomes included the signs of ocular surface disease (OSD) and intraocular pressure (IOP). RESULTS: The adherence of patients treated with the fixed combination was higher than the unfixed treatment at the 3-month (78.0% vs. 63.0%, p < 0.001) and at the 6-month visits (73.0% vs. 58.5%, p < 0.01). The Break-up Time, Schirmer test, and Van Bijsterveld score were worse in the unfixed group at baseline and all subsequent examinations (p < 0.05 for all comparisons). There were no differences in the mean IOP between groups at baseline, 1-, and 3-month visits. IOP appears higher in the unfixed group at 6 months (16.7 vs. 15.0 mmHg, p < 0.01). CONCLUSION: The patients with ocular hypertension and primary open-angle glaucoma treated with a fixed combination are significantly more adherent and show a healthier ocular surface than those treated with an unfixed combination. The study provides significant evidence of the benefits of fixed combination treatment.

A closed-loop audit of the prescription practice of topical antibiotics for acute infective conjunctivitis.

Objective: The implementation of guideline recommendations for antibiotics prescription for the management of patients with acute infective conjunctivitis (AIC) in primary care departments remains below par. Our objective was to assess the impact of clinical audit on adherence to evidence-based indications for prescription of antibiotic eye drops in patients diagnosed with AIC, in the setting of a primary care practice in western Greece. Methods: We conducted a retrospective audit to evaluate the current prescription practice of antibiotics for the management of AIC. Following evidence-based indications for the prescription of antibiotics in AIC through literature search, and in combination with discussion and collaboration with the primary care doctors of our department, we formulated and implemented guidelines for the management of AIC. We then performed a prospective re-audit to assess the management of patients with AIC after local implementation of the guidelines. Results: A total of 158 cases were audited in the first cycle before the introduction of the guidelines, from 15th June 2019 to 7th March 2020, and 26 cases after, from 10th March 2020 to 20th November 2020. The compliance with the guidelines regarding antibiotics prescription was significantly improved from 12.0% to 84.6% between the first and the second cycles of audit. Conclusions: In this study, with the local introduction of guidelines, clinical audit significantly improved the prescription practice of topical antibiotics in patients with AIC in a primary care department. Abbreviations: AIC = acute infective conjunctivitis.

Cardiotoxicity of Chemical Substances: An Emerging Hazard Class.

(1) Background: Human health risks and hazards from chemical substances are well regulated internationally. However, cardiotoxicity, is not defined as a stand-alone hazard and therefore there are no defined criteria for the classification of substances as cardiotoxic. Identifying and regulating substances that cause cardiovascular adverse effects would undoubtedly strengthen the national health systems. (2) Methods: To overcome the aforementioned gap, a roadmap is proposed for identifying regulatory criteria from animal studies and endorse legislation in order to classify substances as cardiotoxic. The roadmap consists of: (i) the identification of the appropriate animal species and strains; (ii) the identification of the lines of scientific evidence (e.g., histopathological, biochemical and echocardiographic indices etc.) from animal studies with relevance to humans; (iii) the statistical analysis and meta-analysis for each line of scientific evidence after exposure to well-established cardiotoxicants to humans (e.g., anthracyclines) in order to identify threshold values or range of normal and/ or altered values due to exposure; (iv) validation of the above described lines of evidence in animals exposed to other alleged cardiotoxic substances (e.g., anabolic androgen steroids (AAS) and pesticides); (v) establishment of mechanisms of action based on information of either known or alleged cardiotoxicants; and (vi) introduction of novel indices and in silico methods. (3) Results: Preliminary results in rats indicate a clear distinction from normal values to values measured in rats exposed to anthracyclines regarding left ventricle (LV) fractional shortening (FS) and LV ejection fraction (EF). A distinctive pattern is similarly observed for Creatine Kinase-Myocardial Band isoenzyme (CK-MB) and cardiac tissue glutathione (GSH). These findings are encouraging and indicate that there is room for targeted research to this end, and that these specific indices and biochemical markers should be further investigated in order to be developed to regulatory criteria. (4) Conclusions: Further research should be conducted by both the scientific and regulatory community that aims to clearly define the cardiotoxicity hazard caused by chemicals and develop a full set of scientific criteria.

Children and Parents' Awareness Regarding Potential Hazards Derived from the Use of Chemical Products in Greece.

Over the last decades, human activities prompted the high production and widespread use of household chemical products, leading to daily exposure of humans to several chemicals. The objective of this study was to investigate the frequency of chemicals' use by children and parents in Greece and estimate the level of risk awareness and understanding among them. A total of 575 parents and children were asked to answer an anonymous, closed-ended, validated, and self-administered questionnaire. One-third of the children and almost half of the parents participating in the study believed that commonly used chemical products do not pose any risk to human health or to the environment, despite the product labelling. The majority of both children (61.8%) and parents (70.6%) were informed about product safety via the product labelling. Around 20% in both groups could not differentiate between systemic toxicity and acute lethal effects depicted by pictograms on the label and milder hazards, such as skin irritation. Moreover, the information on hazard and precautionary statements appearing on the label was very poorly perceived. Therefore, as both children and parents seem not to clearly identify the hazards and risks arising from the use of everyday chemical products, targeted awareness policies should be implemented to support the safe use of household products.

[Corrigendum] What is considered cardiotoxicity of anthracyclines in animal studies.

Subsequently to the publication of this paper, the authors have realized that the name of the seventh listed author, Dimitrios Stagos, was spelt incorrectly (it appeared as 'Stagkos' in print). The corrected author list is shown above. The authors regret that the name of the seventh author on the paper was spelt incorrectly, and apologize to the readers for any inconvenience caused.[the original article was published in Oncology Reports 44: 798-818, 2020; DOI: 10.3892/or.2020.7688].

What is considered cardiotoxicity of anthracyclines in animal studies.

Anthracyclines are commonly used anticancer drugs with well­known and extensively studied cardiotoxic effects in humans. In the clinical setting guidelines for assessing cardiotoxicity are well­established with important therapeutic implications. Cardiotoxicity in terms of impairment of cardiac function is largely diagnosed by echocardiography and based on objective metrics of cardiac function. Until this day, cardiotoxicity is not an endpoint in the current general toxicology and safety pharmacology preclinical studies, although other classes of drugs apart from anthracyclines, along with everyday chemicals have been shown to manifest cardiotoxic properties. Also, in the relevant literature there are not well­established objective criteria or reference values in order to uniformly characterize cardiotoxic adverse effects in animal models. This in depth review focuses on the evaluation of two important echocardiographic indices, namely ejection fraction and fractional shortening, in the literature concerning anthracycline administration to rats as the reference laboratory animal model. The analysis of the gathered data gives promising results and solid prospects for both, defining anthracycline cardiotoxicity objective values and delineating the guidelines for assessing cardiotoxicity as a separate hazard class in animal preclinical studies for regulatory purposes.

Pesticides and cardiotoxicity. Where do we stand?

Cardiovascular diseases are among the most significant causes of mortality in humans. Pesticides toxicity and risk for human health are controlled at a European level through a well-developed regulatory network, but cardiotoxicity is not described as a separate hazard class. Specific classification criteria should be developed within the frame of Regulation (EC) No 1272/2008 in order to classify chemicals as cardiotoxic, if applicable to avoid long-term cardiovascular complications. The aim of this study was to review the cardiac pathology and function impairment due to exposure to pesticides (i.e. organophosphates, organothiophisphates, organochlorines, carbamates, pyrethroids, dipyridyl herbicides, triazoles, triazines) based on both animal and human data. The majority of human data on cardiotoxicity of pesticides come from poisoning cases and epidemiological data. Several cardiovascular complications have been reported in animal models including electrocardiogram abnormalities, myocardial infarction, impaired systolic and diastolic performance, functional remodeling and histopathological findings, such as haemorrhage, vacuolisation, signs of apoptosis and degeneration.

The application of new HARD-descriptor available from the CORAL software to building up NOAEL models.

Continuous QSAR models have been developed and validated for the prediction of no-observed-adverse-effect (NOAEL) in rats, using training and test sets from the Fraunhofer RepDose® database and EFSA's Chemical Hazards Database: OpenFoodTox. This paper demonstrates that the HARD index, as an integrated attribute of SMILES, improves the prediction power of NOAEL values using the continuous QSAR models and Monte Carlo simulations. The HARD-index is a line of eleven symbols, which represents the presence, or absence of eight chemical elements (nitrogen, oxygen, sulfur, phosphorus, fluorine, chlorine, bromine, and iodine) and different kinds of chemical bonds (double bond, triple bond, and stereo chemical bond). Optimal molecular descriptors calculated with the Monte Carlo technique (maximization of correlation coefficient between the descriptor and endpoint) give satisfactory predictive models for NOAEL. Optimal molecular descriptors calculated in this way with the Monte Carlo technique (maximization of correlation coefficient between the descriptor and endpoint) give amongst the best results available in the literature. The models are built up in accordance with OECD principles.

QSAR models for predicting acute toxicity of pesticides in rainbow trout using the CORAL software and EFSA's OpenFoodTox database.

Optimal (flexible) descriptors were used to establish quantitative structure - activity relationships (QSAR) for toxicity of pesticides (n=116) towards rainbow trout. A heterogeneous set of hundreds of pesticides has been used, taken from the EFSA's chemical Hazards Database: OpenFoodTox. Optimal descriptors are preparing from simplified molecular input-line entry system (SMILES). So-called, correlation weights of different fragments of SMILES are calculating by the Monte Carlo optimization procedure where correlation coefficient between endpoint and optimal descriptor plays role of the target function. Having maximum of the correlation coefficient for the training set, one can suggest that the optimal descriptor calculated with these correlation weights can correlate with endpoint for external validation set. This approach was checked up with three different distributions into the training (≈85%) set and external validation (≈15%) set. The statistical characteristics of these models are (i) for training set correlation coefficient (r2) ranges 0.72-0.81, and root mean squared error (RMSE) ranges 0.54-1.25; (ii) for external (validation) set r2 ranges 0.74-0.84; and RMSE ranges 0.64-0.75. Computational experiments have shown that presence of chlorine, fluorine, sulfur, and aromatic fragments is promoter of increase for the toxicity.

Clarification of some aspects related to genotoxicity assessment.

The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow-up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight-of-evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health-based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re-assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight-of-evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight-of-evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. However, if concerns for genotoxicity remain, establishing health-based guidance values is not considered appropriate.

Guidance on the assessment of the biological relevance of data in scientific assessments.

EFSA requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a beneficial health effect) or not. The guidance document provides a general framework for establishing the biological relevance of observations at various stages of the assessment. Biological relevance is considered at three main stages related to the process of dealing with evidence: Development of the assessment strategy. In this context, specification of agents, effects, subjects and conditions in relation to the assessment question(s): Collection and extraction of data; Appraisal and integration of the relevance of the agents, subjects, effects and conditions, i.e. reviewing dimensions of biological relevance for each data set. A decision tree is developed to assist in the collection, identification and appraisal of relevant data for a given specific assessment question to be answered.

Guidance on the use of the weight of evidence approach in scientific assessments.

EFSA requested the Scientific Committee to develop a guidance document on the use of the weight of evidence approach in scientific assessments for use in all areas under EFSA's remit. The guidance document addresses the use of weight of evidence approaches in scientific assessments using both qualitative and quantitative approaches. Several case studies covering the various areas under EFSA's remit are annexed to the guidance document to illustrate the applicability of the proposed approach. Weight of evidence assessment is defined in this guidance as a process in which evidence is integrated to determine the relative support for possible answers to a question. This document considers the weight of evidence assessment as comprising three basic steps: (1) assembling the evidence into lines of evidence of similar type, (2) weighing the evidence, (3) integrating the evidence. The present document identifies reliability, relevance and consistency as three basic considerations for weighing evidence.

Synthetic and Natural Nutritional Supplements: Health "Allies" or Risks to Public Health?

BACKGROUND: The modern way of life involves high stress levels, poor eating habits, lack of exercise, obesity and other detrimental health factors. Nutritional supplements (NS) are complexes of nutrients with variant activity that may infer reversal to nutrient depletion. They tend to be popular amongst social categories associated with the healthy life style, such as the elite and amateur athletes, military people and the general population. OBJECTIVE: An overview of the state of play with regard to nutritional supplements - natural and synthetic-, is important both from toxicological and commercial point of view. METHOD: From a thorough literature review on nutritional supplements, several patents of application have been identified and herewith reviewed which recommend natural vegetable extracts as food supplements for prophylaxis, therapy, protection of immune system, diabetes, oxidative stress, cancer, chronic inflammations and other health conditions. Besides, nutritional supplements of pharmacological validity and high popularity are discussed relative to their contents and group of use. RESULTS: Cases of adulteration or unintentional contamination of commercial products with abusing substances (doping substances, narcotics etc.) or toxic compounds (heavy metals, plant toxics) have shed light to the problem of causing recalls of some products by the FDA. CONCLUSION: From the safety/ quality point of view, NS lack of harmonisation and sovereign laws/ institutional controls on the market and their wide commercialization may possibly lead to risks to public health.

Experimental application of tissue adhesives in corneal traumas.

OBJECTIVE: To evaluate intraoperative difficulties of the use of glues for corneal trauma.
 METHODS: Partial or full-thickness perpendicular corneal incisions (3-4 mm straight cuts) near the limbus (perpendicular or parallel to it) were made in 8 albino rabbits and were then sealed with fibrin or cyanoacrylate glue. Follow-up examinations were performed under the surgical microscope. Tissue specimens were also taken for light microscopic evaluation. 
 RESULTS: The cyanoacrylate glue polymerized almost immediately after application on the tissue, limiting the ability of the surgeon to oppose the corneal incisions appropriately. The fibrin glue polymerized more gradually, giving enough time for manipulations to reconstruct the wound properly and for removal of excessive glue, especially when the 2 components were applied separately. Excessive glue and crust formation on the eye surface induced irritation.
 CONCLUSIONS: Fibrin glue for the reconstruction of corneal wounds was easier to use than cyanoacrylate glue and caused less glue crust formation on the corneal surface. The speed of polymerization is an important factor. Excessive glue on the cornea was irritating.

Post‒cataract surgery endophthalmitis outbreak caused by multidrug-resistant Pseudomonas aeruginosa.

In June 2010, a severe outbreak of 13 cases of post-cataract surgery endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa occurred. Pulse-field gel electrophoresis in eye isolates found 95% genetic similarity; however, extensive environmental and carriage investigation revealed no source of infection.

Vitreous and serum levels of vascular endothelial growth factor and platelet-derived growth factor and their correlation in patients with non-proliferative diabetic retinopathy and clinically significant macula oedema.

PURPOSE: To investigate possible correlations between vitreous and/or serum levels of platelet-derived growth factor isoforms (PDGF-AA, -AB and -BB) with parameters associated with non-proliferative diabetic retinopathy (NPDR) and clinically significant macula oedema (CSMO); to compare the results to relevant results regarding vascular endothelial growth factor (VEGF), which is an established growth factor affecting NPDR. METHODS: Fifteen patients with NPDR, 31 patients with proliferative diabetic retinopathy (PDR) and 15 non-diabetic patients were included in the study. Vitreous and serum samples were obtained during vitrectomy. PDGF-AA, -AB and -BB, as well as VEGF, were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: PDGF-AA, -AB and -BB and VEGF were all expressed in the serum and vitreous of controls and patients with NPDR. The levels of PDGF-AA, PDGF-AB and VEGF in vitreous were significantly increased in the NPDR group compared to controls, while PDGF-BB levels were significantly decreased in the NPDR group compared to controls. The levels of all PDGF isoforms and VEGF in vitreous were significantly increased in the PDR group compared to the NPDR group. No such differences were evident in serum. PDGF-AA and VEGF correlated significantly to the severity of NPDR. PDGF or VEGF in vitreous of NPDR patients did not correlate with retinal photocoagulation (RP) or the serum levels of haemoglobin A1c (HbA1c). There was no correlation between the vitreous and serum levels of VEGF or PDGF in patients with PDR. Only PDGF-AB vitreous levels correlated significantly with PDGF-BB vitreous levels in the NPDR group. CONCLUSION: It appears that in addition to VEGF, almost all PDGF isoforms in the vitreous are also correlated with NPDR and CSMO.

Changing indications for penetrating keratoplasty in Greece, 1982-2006: a multicenter study.

PURPOSE: To evaluate the leading indications for penetrating keratoplasty (PKP) and their trends in Greece during the period 1982 to 2006. METHODS: Retrospective data review of 1,929 patients (2233 eyes) who underwent PKP in the period between 1982 and 2006 at three cornea transplantation units of three hospitals in Greece (Athens General Hospital, Heraklion University Hospital of Crete, and Thessaloniki University Hospital). Indications were classified into nine different groups: keratoconus, herpes simplex keratitis, microbial (nonviral) keratitis (fungal, bacterial, and acanthamoeba), aphakic/pseudophakic corneal edema, posttraumatic corneal scars, chemical/thermal injury, regraft, Fuchs' endothelial dystrophy, and other. RESULTS: The leading indications for PKP, in order of decreasing frequency, were aphakic/pseudophakic corneal edema (n = 649 [29.1%]), keratoconus (n = 580 [26%]), regraft (n = 265 [11.9%]), microbial (nonviral) keratitis (n = 188 [8.4%]), posttraumatic corneal scar (n = 171 [7.7%]), herpes simplex keratitis (n = 104 [4.6%]), Fuchs' endothelial dystrophy (n = 104 [4.6%]), chemical/thermal injury (n = 61 [2.7%]), and other (n = 111 [5%]). The prevalence of regrafts as an indication for PKP increased during the study period. CONCLUSIONS: Aphakic/pseudophakic corneal edema was the most common indication for PKP in a multicenter series in Greece followed by keratoconus. The number of regrafts dramatically increased during the 25-year period.