Several Years Of Exposure Research Articles

Preliminary human health risk assessment of antibiotic exposures in human waste handling occupations

Exposure to biosolids in human waste handling occupations is associated with a risk for illness due to microbial infections. Although several years of exposure to biosolids might be hypothesized to be a prophylaxis against infection, the risks associated with infections from antibiotic-resistant organisms can also be a potential concern. Therefore, this study aimed to conduct a screening level risk assessment by deriving occupational exposure limits (OELs) characterizing the risks of adverse health effects among workers in human waste handling occupations with a focus on exposure to two pharmaceuticals commonly found in biosolids: ciprofloxacin (CIP) and azithromycin (AZ). Epidemiological and exposure studies of workers exposed to biosolids were identified through searches of major scientific databases. Screening OELs (sOELs) for these antibiotics were derived using a standardized methodology. The airborne concentrations of CIP and AZ antibiotics were determined using an exposure factors approach. The health-based exposure limits (i.e., sOELs) and the acceptable daily exposure (ADE) values for both of these antibiotics were derived as 80 μg/m3 and 12 μg/kg-day, respectively. An exposure factor approach suggested that inhalation route exposures to CIP and AZ are well below the sOELs and ADE daily doses, and likely too low to cause direct adverse health effects through antibiotic inhalation. A critical review of epidemiological studies on different occupations handling biosolids showed that the workers in industries with potential biosolids exposure have experienced an increased incidence of microbial-exposure-related illness. The health effects seen in the workers have been attributed to bacterial, viral, and protozoan infections. To the extent that bacteria are the pathogen of concern, it is not clear whether these bacteria are resistant to antibiotics commonly found in biosolids. It is also unclear whether the presence of antibiotics or antibiotic-resistant bacteria increases the susceptibility of these workers. Additional studies will provide more definitive estimates of inhalation and dermal exposures to CIP and AZ and could verify the exposure estimates in this study based on the literature and common exposure factors.

On radar and radio exposure and cancer in the military setting

IntroductionIn 2018, we reported a case series of 47 patients diagnosed with cancer following several years of exposure to high-intensity whole-body radiofrequency radiation (RFR) using the parameter of percentage frequency (PF). Consistent high and statistically significant PFs of hematolymphoid (HL) cancers were found in this group and in four previous reports on RFR-exposed groups in Belgium, Poland and Israel together with increased all-cancers rates. In this paper we report a new series of 46 young cancer patients who were exposed during military service to such radiation. Materials and methodsThe new group of patients comprises Israeli soldiers previously exposed to occupational RFR. The patients were self-selected to enroll in the research in cooperation with an NGO assisting patients with administrative counseling and legal and social services. The new group of patients was studied with respect to distribution (proportion) of cancer types using the method of PF. When possible, cancer risk ratios (RR) were estimated too. The results are compared to those of other occupational groups in three countries. ResultsMedian age at diagnosis was 23 years; duration of exposure was between 1 and 3 years and the latencies were short, median 4.6 years. The PF of HL cancers was 41.3%, 95% CI (27%–57%), versus 22.7% expected in non-exposed subjects matched for age and gender profiles, p = 0.003; 19 out of the 46 patients had HL cancers. The PF of Hodgkin lymphoma cancers was 21.7%, 95%CI (11%–36%), versus 11.6% expected, p = 0.033. For a subgroup of 6 patients, the number of soldiers in the units was known, and we were able estimate approximately the overall cancer risk ratio (RR) after 8 years as being 8.0 with 95% CI (2.9, 17), p < 0.002, with only 0.75 cases expected from the Cancer Registry data. In this subgroup, there were 3 HL cancer cases and 3 non-HL cases. Sarcoma PF was higher than expected, 7 out of the 46 patients were diagnosed with sarcoma, PF = 15.2%, 95%CI (6.3%–28.9%), p = 0.04 versus the expected PF of 7%. ConclusionThe HL PF was high and consistent with previous reports. Epidemiological studies on excess risk for HL and other cancers, brain tumors in cellphone users, and experimental studies on RFR and carcinogenicity strongly point to a cause-effect relationship. It is mandatory to reduce the RFR exposure of all personnel to that of the typical community levels, including the peak level of radar pulses. Radiation protection, safety instructions, cancer risk warnings and quantitative data on individual exposure together with regular medical monitoring must be instituted for all personnel exposed to such risks. The findings from our study add to the growing body of evidence underscoring the gross inadequacy of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) thermal standards. Based on our findings and on the previous accumulated research, we endorse the recommendations to reclassify RFR exposure as a human carcinogen, International Agency for Research on Cancer (IARC) group 1.

Brain Source Correlates of Speech Perception and Reading Processes in Children With and Without Reading Difficulties.

Neural correlates in reading and speech processing have been addressed extensively in the literature. While reading skills and speech perception have been shown to be associated with each other, their relationship remains debatable. In this study, we investigated reading skills, speech perception, reading, and their correlates with brain source activity in auditory and visual modalities. We used high-density event-related potentials (ERPs), fixation-related potentials (FRPs), and the source reconstruction method. The analysis was conducted on 12–13-year-old schoolchildren who had different reading levels. Brain ERP source indices were computed from frequently repeated Finnish speech stimuli presented in an auditory oddball paradigm. Brain FRP source indices were also computed for words within sentences presented in a reading task. The results showed significant correlations between speech ERP sources and reading scores at the P100 (P1) time range in the left hemisphere and the N250 time range in both hemispheres, and a weaker correlation for visual word processing N170 FRP source(s) in the posterior occipital areas, in the vicinity of the visual word form areas (VWFA). Furthermore, significant brain-to-brain correlations were found between the two modalities, where the speech brain sources of the P1 and N250 responses correlated with the reading N170 response. The results suggest that speech processes are linked to reading fluency and that brain activations to speech are linked to visual brain processes of reading. These results indicate that a relationship between language and reading systems is present even after several years of exposure to print.

Half-lives of several polyfluoroalkyl substances (PFAS) in cattle serum and tissues

ABSTRACT Cattle that were at steady-state serum polyfluoroalkyl substances (PFAS) concentrations due to several years of exposure to water contaminated by residues of Aqueous Film-Forming (AFFF) firefighting foam had perfluorooctane sulphonate (PFOS) isomers, perfluoroheptane sulphonate (PFHpS), perfluorohexane sulphonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in serum. Elimination serum half-lives were determined in five heifers from serial blood sampling over 215 days. Eleven additional animals that had blood sampled on day 19 (d19) were euthanised on d63. PFAS half-life estimates from the serial blood sampling and from d19/d63 data were not significantly different. The combined (n = 16) serum half-lives (in days) were: total PFOS (tPFOS, 74.1 ± 13.4), PFHpS (45.7 ± 9.4), PFHxS (9.3 ± 1.3), PFNA (12.3 ± 3.2) and PFDA (60.4 ± 10.4). The half-lives of linear PFOS (L-PFOS, 69.4 ± 11.6) and mono branched PFOS isomers (m-PFOS, 83.6 ± 19) were not significantly different from tPFOS, but for the di-branched isomers (di-PFOS), the serum half-life was significantly lower (29.9 ± 5.8). Animal age (1.4–12.3 years old) and serum concentration at the start of depuration did not influence half-lives, and there was no difference between steers and heifers. Consideration of serum and tissue PFAS concentrations at d63 and d215 indicated there was no difference in tPFOS depuration from serum or muscle, but elimination from liver and kidney may be slightly longer. Depuration of PFHpS is essentially the same in serum, kidney and liver, and it is expected depletion from muscle would be comparable. The short half-life of di-PFOS, PFHxS and PFNA did not allow an assessment of clearance from tissues because they were not measurable at d215 but based on the results for PFOS and PFHpS, elimination of PFHxS from tissues is expected to mirror that from serum. Human health risk assessment implications are discussed.

Fatigue damage prediction in the annulus of cervical spine intervertebral discs using finite element analysis

Neck pain is a major inhibitor affecting the performance of U.S. military personnel. Repetitive exposure to cyclic loading due to military activities over several years can lead to accumulation of fatigue damage in the cervical intervertebral disc annuli, leading to neck pain. We have developed a computational damage model based on continuum damage mechanics, to predict fatigue damage to cervical disc annuli over several years of exposure to military loading scenarios. By integrating this fatigue damage model with a finite element model of the cervical spine, we have overcome the underlying assumption of a uniform stress distribution in the annulus. The resulting element-wise damage prediction gives us insight into the location of damage initiation and pattern of fatigue damage progression in the cervical disc annulus.

Une cause rare d’altération de l’état général : cardiopathie et myopathie aux antipaludéens de synthèse

IntroductionThis case report signifies the need to systemically assess antimalarial toxicity in those undergoing long-term treatment. Case reportA 59-year-old man with a history of ischemic-labeled heart disease revealed by conduction disorders and cutaneous lupus treated initially with hydroxychloroquine followed by chloroquine consulted for asthenia and weight loss. Clinically, he had a muscular atrophy, a motor deficit, and an abolition of the osteo-tendinous reflexes in the lower limbs. Adverse drug effects of the antimalarial therapy were suspected–specifically, muscular and cardiac toxicity. The diagnosis was confirmed with a muscle biopsy, which showed typical and florid vacuolar myopathy. Cessation of the drug resulted in a slow regression of symptoms. ConclusionCardiac and muscular toxicity related to antimalarials are rare and sometimes fatal; thus, they must be systematically assessed in a patient with several years of exposure. A muscle biopsy could be sufficient to allow for the diagnosis.

Evaluation of anti-soiling coatings for CSP reflectors under realistic outdoor conditions

Soiling of solar reflectors affects their reflectance and has a direct impact on the power output of concentrated solar power (CSP) plants. One way to minimize the efficiency losses is the implementation of anti-soiling coatings on the reflector surfaces. This method is being studied for the past decade, but has not been successfully commercialized yet. The purpose of the coatings is to reduce soiling and improve the washability of the reflectors. In this work results are presented from an extensive outdoor campaign of two potential anti-soiling coatings under realistic conditions at a representative CSP site in southern Spain. Nearly six years of outdoor data are available, which makes this campaign the longest published on this type of coatings. Regular cleaning and reflectance measurements were performed during the exposure and conclusions about the performance and durability of the coatings are drawn. It is shown that in the initial state the coatings show an advantageous behavior, resulting in higher reflectance during outdoor exposure due to less soiling and better cleaning of the reflectors. The second main finding is that durability is an important issue for the implemented coatings, as their properties degrade over time resulting in lower reflectance values after several years of exposure compared to conventional glass reflectors.

Determination of Toxic Metals Content in Iranian and Italian Flavoured Olive Oil

Abstract Cultural practices and control of diseases and insects are widely used for cultivation of Olea europea L. These are considered potential contaminants. Aim of this investigation lies in determination of concentrations of contaminants in several edible olive oils. All test samples were purchased in three consecutive seasons. They were analysed in compliance with standardized international protocols of wet digestion methods. Ion concentrations were determined in three replicates using method of inductively coupled plasma optical emission spectrometry. We have registered a positive correlation between storage time and heavy metals contents. It was particularly high in Iranian brands and varied significantly. Investigation results show that all obtained heavy metals contents in pepper-flavoured olive oil samples were significantly lower than in other samples. Considering the fungi-flavoured samples, levels of Pb and Cd were prominent and exceeded the maximum permissible level set in the majority of cases. The further monitoring is needed as all these metals are toxic and their detrimental effect becomes obvious only after several years of exposure.

Impermeable membranes for slab-track settlement mitigation

A series of numerical simulations is used to explore the effect of the geometrical disposition of impermeable membranes in the overall performance of slab-track railway earthworks, with particular reference to the generation of settlement during several years of exposure to the atmosphere and the admissibility of these post-construction deformations according to the available standards. A methodology suitable to account for the effects of rail traffic loading and environmental actions over its service life is presented. To emphasise the effect of the water-impermeable membranes on the atmospheric-induced embankment irreversible deformations, both semi-arid and wet climate conditions were investigated, making use of real climate data for a period of 10 years. The numerical results show that the calculated settlement can be beyond the admissible values and that the use of impermeable membranes is an available alternative for its mitigation.

Tendinous tissue properties after short‐ and long‐term functional overload: Differences between controls, 12 weeks and 4 years of resistance training

The potential for tendinous tissues to adapt to functional overload, especially after several years of exposure to heavy-resistance training, is largely unexplored. This study compared the morphological and mechanical characteristics of the patellar tendon and knee extensor tendon-aponeurosis complex between young men exposed to long-term (4years; n=16), short-term (12weeks; n=15) and no (untrained controls; n=39) functional overload in the form of heavy-resistance training. Patellar tendon cross-sectional area, vastus lateralis aponeurosis area and quadriceps femoris volume, plus patellar tendon stiffness and Young's modulus, and tendon-aponeurosis complex stiffness, were quantified with MRI, dynamometry and ultrasonography. As expected, long-term trained had greater muscle strength and volume (+58% and +56% vs untrained, both P<.001), as well as a greater aponeurosis area (+17% vs untrained, P<.01), but tendon cross-sectional area (mean and regional) was not different between groups. Only long-term trained had reduced patellar tendon elongation/strain over the whole force/stress range, whilst both short-term and long-term overload groups had similarly greater stiffness/Young's modulus at high force/stress (short-term +25/22%, and long-term +17/23% vs untrained; all P<.05). Tendon-aponeurosis complex stiffness was not different between groups (ANOVA, P=.149). Despite large differences in muscle strength and size, years of resistance training did not induce tendon hypertrophy. Both short-term and long-term overload demonstrated similar increases in high-force mechanical and material stiffness, but reduced elongation/strain over the whole force/stress range occurred only after years of overload, indicating a force/strain specific time-course to these adaptations.

Chloride Resistance of Nanoparticle Repaired Concrete Measured by Accelerated Tests

This paper describes results of experimental investigation of chloride ion penetration in concrete. Chloride concentration have been studied in accelerated conditions. Part of concrete samples were treated with colloidal nanosilica solution to increase their resistance to further chloride penetration. Measurement of chloride profiles was performed and compared on samples subjected to accelerated electrical migration tests lasting for a few days. The chloride ion profile in samples was determined in layers of 5 mm thickness up to a total profile thickness of 45 mm. The developed chloride concentrations reached values found after several years of exposure in natural conditions. It was found that the resistance to chloride penetration is substantially improved by nanosilica injection and the resistance to chloride penetration is increased by 60%.

The impact of 5 years’ underwater exposure in the Baltic Sea (Puck Bay) on selected properties of English oak wood samples

In order to understand the influence of the underwater marine environment on changes in selected properties of contemporary wood, samples of oak wood were tested following several years of exposure at an underwater archaeological site (Puck Bay, Baltic Sea). The content of the major and minor components of the wood, as well as the total amount of minerals were determined. Selected physical properties were tested, as well as the strength and resistance of marine wood to rot caused by Basidiomycetes fungi. The study showed a decrease in the strength of the wood, changes in the chemical composition, and an increase in the quantity of mineral substances. In addition, a marked increase was found in the susceptibility of the tested wood to degradation by Basidiomycetes. These results indicate that the immersion of oak wood in the waters of Puck Bay caused significant changes in its physical, chemical and biological properties. Observations of changes occurring in contemporary wood can be useful in the monitoring of underwater archaeological sites.

Long-term performance of glass-powder concrete in large-scale field applications

Development of local alternative supplementary-cementitious materials (ASCM) such as ground mixed-waste glass is demanded especially when other ASCM are not locally available or costly. The promising performance of glass powder (GP) in concrete mixtures in laboratory scale motivated the current study that focussed on presenting the long-term performance of GP-concrete in large-scale field applications. The evaluated structural elements (constructed between 2006 and 2011) included interior and exterior slabs and walls. The results of core samples extracted from the structural elements after several years of exposure were compared to the laboratory-cured samples taken at the time of casting. The 6.7-year core results showed a continuous improvement in the mechanical performance and resistance chloride-ion penetration of the GP concrete due to its pozzolanic reactivity. The water absorption of and porosity were also decreased obtained when using GP due to the microstructure densification.

Meeting the threshold of multifunctional CD8+ TEM by γ-irradiated sporozoite vaccination, essential to ensue sterile protection against Plasmodia liver stage infection

Abstract People in malaria endemic area develop immunity after several years of exposure to parasite, children particularly take longer to develop protective immunity. Interestingly, the protection is lot more consistent among children living in high transmission area compared to those of low transmission area, suggesting that protection may depend on the frequency of exposure and/or a load of parasite exposure. Thus, we hypothesize children experiencing multiple exposures might develop critical frequencies of anti-parasite lymphocytes ensuring the protection to Plasmodia. CD8+ T cells play a key role in mediating protection against Plasmodia liver-stage infection. In present study, we took whole sporozoite (spz) vaccination strategy and immunized C57Bl/6 mice with multiple doses of γ-spz at different time intervals. We found continuous immunization with 3 and 4 doses of γ-spz, 2 weeks apart, provides ~50% and 100% sterile protection, respectively. However, mice immunized with 3 doses of γ-spz with an interval of 90 days during 2nd – 3rd dose fail to be protected. Upon measuring the CD8+ T cell responses, we found that higher frequencies of liver-stage specific multifunctional CD8+ T cells (CD44hiKLRG-1intCD107+IFN-γ+) were accumulated in mice immunized with 4 doses of γ-spz (180–410 cells/106; Avg. 284), whereas the same among mice receiving 3 doses showed lower frequencies (50–125 cells/106; Avg. 75) before challenge, and mixed frequencies (126–551 cells/106; Avg. 340) following challenge, suggesting that protection against Plasmodia infection could be ensured either by pre-existing multifunctional memory CD8+ T cells before the infection or mobilizing the required frequencies of the same to liver during the course of infection.

Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field

The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg−1 soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg−1 macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg−1 macrolides. Rapid mineralization of 14C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance.

Condition assessment of reinforced concrete structures subject to chloride ingress: A case study of updating the model prediction considering inspection data

The durability of reinforced concrete structures is affected by the corrosion of steel reinforcement due to chloride ingress. In general, the service life of a reinforced concrete structure is determined by considering the time to initiate and the time to propagate corrosion. Probabilistic models have been used to estimate the service life of a concrete structure by taking into account the inherent randomness observed in this process. Within this aim, it is vital to inspect the structure after several years of exposure using destructive or non-destructive testing to update the service life prediction models and to schedule proactive maintenance. This paper discusses a case study to analyze inspection data (i.e. potential mapping) to update the condition of the structure using a probabilistic service life prediction model. It also discusses the effect of the variation of water/cement (w/c) ratio on updated model prediction probabilities.

First- and final-semester non-native students in an English-medium university: Judgments of their speech by university peers

By the end of their studies, non-native speakers of English studying at English-medium universities have had several years of exposure to English in that setting. Do non-native students, particularly those enrolled in non-languagerelated programs, show different levels of second language (L2) speaking ability in their final semester of studies than non-native students in their first semester, as judged by other students in the university community? In this exploratory cross-sectional study, two matched groups of L2 English university students in their first or final semester of study in non-language-related programs ( N = 20) were recorded in mock job interviews. The students were rated by two groups of raters for accentedness, comprehensibility, fluency, and communicative effectiveness. Both rater groups were university students; one group was from diverse academic programs, while the other group was studying human resource management (HRM). Although the first- and final-semester L2 English students differed in how long they had studied in English, no significant difference in ratings between first- and final-semester students was found. However, the two rater groups differed in how they rated accentedness and comprehensibility, suggesting that the nature of listeners' previous academic experience (e.g., with HRM) influences their judgments. The use of holistic rating scales to evaluate L2 speech is discussed, as well as the relationship between the nature of language exposure and the performance of the student and rater groups.

Damage accumulation location under cyclic loading in the lumbar disc shifts from inner annulus lamellae to peripheral annulus with increasing disc degeneration

It is difficult to study the breakdown of lumbar disc tissue over several years of exposure to bending and lifting by experimental methods. In our earlier published study we have shown how a finite element model of a healthy lumbar motion segment was used to predict the damage accumulation location and number of cyclic to failure under different loading conditions. The aim of the current study was to extend the continuum damage mechanics formulation to the degenerated discs and investigate the initiation and progression of mechanical damage. Healthy disc model was modified to represent degenerative discs (Thompson grade III and IV) by incorporating both geometrical and biochemical changes due to degeneration. Analyses predicted decrease in the number of cycles to failure with increasing severity of disc degeneration. The study showed that the damage initiated at the posterior inner annulus adjacent to the endplates and propagated outwards towards its periphery in healthy and grade III degenerated discs. The damage accumulated preferentially in the posterior region of the annulus. However in grade IV degenerated disc damage initiated at the posterior outer periphery of the annulus and propagated circumferentially. The finite element model predictions were consistent with the infrequent occurrence of rim lesions at early age but a much higher incidence in severely degenerated discs.

A Cross-linguistic Perspective on Questions in German and French Adult Second Language Acquisition

Several studies have been conducted to try and understand and explain the morphological and syntactic aspects of adult second language acquisition (SLA). Two prominent hypotheses that have been put forward concerning late L2 speakers' knowledge of inflectional morphology and of related functional categories and their feature values are the Impaired Representation Hypothesis (IRH) and the Missing Surface Inflection Hypothesis (MSIH). The cross-linguistic comparison of the acquisition of questions in German and French provided in this study offers a new perspective to differences and similarities between first language acquisition (FLA) and adult SLA. Comparing a Germanic and a Romance L2, differing not only in their overall linguistic properties (such as i. e. OV/VO, V2, clitics), but explicitly in the formation and regularities of questions, we present striking similarities in adult SLA, and irrespective of the first and the second languages and of instructed versus non-instructed learning. The investigation of the adult SLA of morphological and structural aspects of questions in French and German strengthens the assumption that the acquisition of morphology and syntax is connected in French and German FLA but is disentangled in adult SLA. Our data reveal variability of question syntax, and with the syntactic position of the verb in particular. Instead of discovering the correct position of the verb at a certain stage of acquisition which can be accounted for by parameter setting in FLA, the adult learners gradually approach the target word order but still exhibit a great deal of variation after several years of exposure to the L2. The findings provided here contradict the predictions of the MSIH (Prévost/White 2000; Ionin/Wexler 2002; among others), for not only morphological features, but syntactic finiteness of finiteness are problematic in adult SLA, and that the Impairment Representation Hypothesis (IRH) (Beck 1998; Eubank 1993/1994; among others) accounts for these differences in first and second language acquisition. IRH and FDH mirror our findings, by predicting the use of (domain-general) strategies instead of agreement or feature checking mechanisms.

Cancer Risk of Anti-TNF-α at Recommended Doses in Adult Rheumatoid Arthritis: A Meta-Analysis with Intention to Treat and per Protocol Analyses

BackgroundThe risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown.Methodology/Principal FindingsData sources were MEDLINE, CENTRAL, ISI Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the drugs leading to their marketing approval, and clinicaltrials.gov, until 31 December 2012.We selected double-blind randomized controlled trials in adult rheumatoid arthritis patients, including at least one treatment arm in line with New Drug Application. We performed random effect meta-analysis, with modified intention to treat and per protocol analyses. Thirty-three trials were included. There was no excess risk of malignancies on anti-TNF-α administered in line with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59–1.44]), as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82–1.98]). There was a non-significant tendency for an excess non-melanoma skin cancer risk in both models (respectively, 1.37 [0.71–2.66] and 1.90 [0.98–3.67]). With fixed effect Peto model restricting to trials during at least 52 weeks, the overall cancer risk was respectively 1.60 [0.97–2.64] and 1.22 [0.72–2.08]. Whatever the model, modified intention to treat analysis led to higher estimations than per protocol analysis. The later may underestimate the treatment effect when assessing very sparse events and when many patients dropped out in placebo arms. In metaregression, there was no differential risk among the five drugs.Conclusions/SignificanceThis study did not find any evidence for an excess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, but an excess cancer risk after several years of exposure cannot be ruled out. Both modified intention to treat and per protocol analyses should be presented in such safety analyses.