Parental occupational exposure to organic solvents and anencephaly in Mexico

Objective: To assess the relationship between parental occupational exposure to organic solvents, and the risk of anencephaly in Mexico. Methods: A case-control study was conducted based on the registers of the Epidemiological Surveillance System for Neural Tube Defects in Mexico; 151 cases of anencephaly of ≥20 weeks’ gestation were included. A control, born alive and without any apparent congenital malformations at birth, was selected for each case in the same maternity service in which the case was born. Information on occupational exposures, lifestyle habits, reproductive history, use of medicines, supplementation with multivitamins and folic acid, was obtained by a general questionnaire; a food frequency questionnaire was also applied to obtain information of daily intake of folate and other B vitamins. Occupational exposure to organic solvents was based on job title as a proxy for exposure and analysed considering two critical periods around conception. Results: In logistic regression analysis, the odds of having a child with anencephaly was higher if the mother or the father was occupationally exposed to organic solvents during the periconceptional period, or when both parents or at least one of them were occupationally exposed during this period with an adjusted odds ratio of 2.97 (95% CI 1.36 to 6.52). Conclusions: The results support the hypothesis that both maternal and paternal occupational exposure to organic solvents can increase the probability of having a child with anencephaly.

Air pollution exposure during pregnancy and reduced birth size: a prospective birth cohort study in Valencia, Spain

Background Maternal exposure to air pollution has been related to fetal growth in a number of recent scientific studies. The objective of this study was to assess the association between exposure to air pollution during pregnancy and anthropometric measures at birth in a cohort in Valencia, Spain. Methods Seven hundred and eighty-five pregnant women and their singleton newborns participated in the study. Exposure to ambient nitrogen dioxide (NO2) was estimated by means of land use regression. NO2 spatial estimations were adjusted to correspond to relevant pregnancy periods (whole pregnancy and trimesters) for each woman. Outcome variables were birth weight, length, and head circumference (HC), along with being small for gestational age (SGA). The association between exposure to residential outdoor NO2 and outcomes was assessed controlling for potential confounders and examining the shape of the relationship using generalized additive models (GAM). Results For continuous anthropometric measures, GAM indicated a change in slope at NO2 concentrations of around 40 μg/m3. NO2 exposure >40 μg/m3 during the first trimester was associated with a change in birth length of -0.27 cm (95% CI: -0.51 to -0.03) and with a change in birth weight of -40.3 grams (-96.3 to 15.6); the same exposure throughout the whole pregnancy was associated with a change in birth HC of -0.17 cm (-0.34 to -0.003). The shape of the relation was seen to be roughly linear for the risk of being SGA. A 10 μg/m3 increase in NO2 during the second trimester was associated with being SGA-weight, odds ratio (OR): 1.37 (1.01-1.85). For SGA-length the estimate for the same comparison was OR: 1.42 (0.89-2.25). Conclusions Prenatal exposure to traffic-related air pollution may reduce fetal growth. Findings from this study provide further evidence of the need for developing strategies to reduce air pollution in order to prevent risks to fetal health and development.

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung: a dialog between aerosol science and biology

The introduction of engineered nanostructured materials into a rapidly increasing number of industrial and consumer products will result in enhanced exposure to engineered nanoparticles. Workplace exposure has been identified as the most likely source of uncontrolled inhalation of engineered aerosolized nanoparticles, but release of engineered nanoparticles may occur at any stage of the lifecycle of (consumer) products. The dynamic development of nanomaterials with possibly unknown toxicological effects poses a challenge for the assessment of nanoparticle induced toxicity and safety.In this consensus document from a workshop on in-vitro cell systems for nanoparticle toxicity testing11Workshop on 'In-Vitro Exposure Studies for Toxicity Testing of Engineered Nanoparticles' sponsored by the Association for Aerosol Research (GAeF), 5-6 September 2009, Karlsruhe, Germany. an overview is given of the main issues concerning exposure to airborne nanoparticles, lung physiology, biological mechanisms of (adverse) action, in-vitro cell exposure systems, realistic tissue doses, risk assessment and social aspects of nanotechnology. The workshop participants recognized the large potential of in-vitro cell exposure systems for reliable, high-throughput screening of nanoparticle toxicity. For the investigation of lung toxicity, a strong preference was expressed for air-liquid interface (ALI) cell exposure systems (rather than submerged cell exposure systems) as they more closely resemble in-vivo conditions in the lungs and they allow for unaltered and dosimetrically accurate delivery of aerosolized nanoparticles to the cells. An important aspect, which is frequently overlooked, is the comparison of typically used in-vitro dose levels with realistic in-vivo nanoparticle doses in the lung. If we consider average ambient urban exposure and occupational exposure at 5mg/m3 (maximum level allowed by Occupational Safety and Health Administration (OSHA)) as the boundaries of human exposure, the corresponding upper-limit range of nanoparticle flux delivered to the lung tissue is 3×10-5-5×10-3μg/h/cm2 of lung tissue and 2-300particles/h/(epithelial) cell. This range can be easily matched and even exceeded by almost all currently available cell exposure systems.The consensus statement includes a set of recommendations for conducting in-vitro cell exposure studies with pulmonary cell systems and identifies urgent needs for future development. As these issues are crucial for the introduction of safe nanomaterials into the marketplace and the living environment, they deserve more attention and more interaction between biologists and aerosol scientists. The members of the workshop believe that further advances in in-vitro cell exposure studies would be greatly facilitated by a more active role of the aerosol scientists. The technical know-how for developing and running ALI in-vitro exposure systems is available in the aerosol community and at the same time biologists/toxicologists are required for proper assessment of the biological impact of nanoparticles.

Catastrophic medical expenditure risk

Medical expenditure risk can pose a major threat to living standards. We derive decomposable measures of catastrophic medical expenditure risk from reference-dependent utility with loss aversion. We propose a quantile regression based method of estimating risk exposure from cross-section data containing information on the means of financing health payments. We estimate medical expenditure risk in seven Asian countries and find it is highest in Laos and China, and is lowest in Malaysia. Exposure to risk is generally higher for households that have less recourse to self-insurance, lower incomes, wealth and education, and suffer from chronic illness.

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

Leprosy exposure, infection and disease: a 25-year surveillance study of leprosy patient contacts

Contact surveillance is a valuable strategy for controlling leprosy. A dynamic cohort study of leprosy contacts was initiated in 1987 at Oswaldo Cruz Foundation. The objective of this work was to review the data on the major risk factors leading up to the infectious stage of the disease, estimate incidence rates of leprosy in the cohort and characterise the risk factors for the disease among the contacts under surveillance. The incidence rate of leprosy among contacts of leprosy patients was estimated at 0.01694 cases per person-year in the first five years of follow-up. The following factors were associated with acquiring the disease: (i) not receiving the BCG vaccine, (ii) a negative Mitsuda reaction and (iii) contact with a patient with a multibacillary clinical form of leprosy. The contacts of index patients who had high bacilloscopic index scores > 1 were at especially high risk of infection. The following factors were associated with infection, which was defined as a seropositive reaction for anti-phenolic glicolipid-1 IgM: (i) young age (< 20 years), (ii) a low measured Mitsuda reaction (< 5 mm) and (iii) contact with an index patient who had a high bacilloscopic index. BCG vaccination and re-vaccination were shown to be protective among household contacts. The main conclusions of this study indicate an urgent need for additional leprosy control strategies in areas with a high incidence of the disease.

Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).

Given the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.

Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.

BACKGROUND: Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficiency virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. METHODS: We evaluated the contribution of 22 SNPs identified in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. RESULTS: The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidence interval [CI], 2.05-7.06) and 2.74 (95% CI, 1.53-4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. CONCLUSIONS: In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantly to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

Influenza A virus infection of healthy piglets in an abattoir in Brazil: animal-human interface and risk for interspecies transmission

Asymptomatic influenza virus infections in pigs are frequent and the lack of measures for controlling viral spread facilitates the circulation of different virus strains between pigs. The goal of this study was to demonstrate the circulation of influenza A virus strains among asymptomatic piglets in an abattoir in Brazil and discuss the potential public health impacts. Tracheal samples (n = 330) were collected from asymptomatic animals by a veterinarian that also performed visual lung tissue examinations. No slaughtered animals presented with any noticeable macroscopic signs of influenza infection following examination of lung tissues. Samples were then analysed by reverse transcription-polymerase chain reaction that resulted in the identification of 30 (9%) influenza A positive samples. The presence of asymptomatic pig infections suggested that these animals could facilitate virus dissemination and act as a source of infection for the herd, thereby enabling the emergence of influenza outbreaks associated with significant economic losses. Furthermore, the continuous exposure of the farm and abattoir workers to the virus increases the risk for interspecies transmission. Monitoring measures of swine influenza virus infections and vaccination and monitoring of employees for influenza infection should also be considered. In addition regulatory agencies should consider the public health ramifications regarding the potential zoonotic viral transmission between humans and pigs.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.

Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.

BACKGROUND The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. METHODS We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. RESULTS Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older (>50 years) strata increased significantly (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By competing risk analysis women started ART earlier than men (adjusted subhazard ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of these differences were observed. In both cohorts women showed a shorter time to the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and patient's/physician's decisions as reasons for changing were more frequent in women than in men in CoRIS. In the Cox regression model, gender was not associated with differences in survival. CONCLUSIONS In two large cohorts in Spain, we observed relevant gender differences in epidemiological characteristics and antiretroviral exposure outcomes, while survival differences were not attributable to gender.

Risk factors associated with Trypanosoma cruziexposure in domestic dogs from a rural community in Panama

Chagas disease, caused by Trypanosoma cruzi infection, is a zoonosis of humans, wild and domestic mammals, including dogs. In Panama, the main T. cruzi vector is Rhodnius pallescens, a triatomine bug whose main natural habitat is the royal palm, Attalea butyracea. In this paper, we present results from three T. cruzi serological tests (immunochromatographic dipstick, indirect immunofluorescence and ELISA) performed in 51 dogs from 24 houses in Trinidad de Las Minas, western Panama. We found that nine dogs were seropositive (17.6% prevalence). Dogs were 1.6 times more likely to become T. cruziseropositive with each year of age and 11.6 times if royal palms where present in the peridomiciliary area of the dog’s household or its two nearest neighbours. Mouse-baited-adhesive traps were employed to evaluate 12 peridomestic royal palms. All palms were found infested with R. pallescens with an average of 25.50 triatomines captured per palm. Of 35 adult bugs analysed, 88.6% showed protozoa flagellates in their intestinal contents. In addition, dogs were five times more likely to be infected by the presence of an additional domestic animal species in the dog’s peridomiciliary environment. Our results suggest that interventions focused on royal palms might reduce the exposure to T. cruzi infection.

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: preliminary data from year 9 of the follow-up.

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01-1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.

Ganciclovir exposure under a 450mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study.

Manuel O, Pascual M, Perrottet N, Lamoth F, Venetz J-P, Decosterd LA, Buclin T, Meylan PR. Ganciclovir exposure under a 450 mg daily dosage of valganciclovir for cytomegalovirus prevention in kidney transplantation: a prospective study. 
Clin Transplant 2010: 24: 794-800. Abstract:  This prospective study aimed at determining the ganciclovir exposure observed under a daily dosage of 450 mg valganciclovir routinely applied to kidney transplant recipients with a GFR above 25 mL/min at risk for cytomegalovirus (CMV) disease. Ganciclovir levels at trough (C(trough) ) and at peak (C(3 h) ) were measured monthly. Ganciclovir exposure (area under the curve [AUC(0-24) ]) was estimated using Bayesian non-linear mixed-effect modeling (NONMEM). Thirty-six patients received 450 mg of valganciclovir daily for three months. Median ganciclovir C(3 h) was 3.9 mg/L (range: 1.3-7.1), and C(trough) was 0.4 mg/L (range 0.1-2.7). Median AUC(0-24) of ganciclovir was 59.3 mg h/L (39.0-85.3) in patients with GFR(MDRD) 26-39 mL/min, 35.8 mg h/L (24.9-55.8) in patients with GFR(MDRD) 40-59 mL/min, and 29.6 mg h/L (22.0-43.2) in patients with GFR(MDRD)  ≥ 60 mL/min. No major differences in adverse events according to ganciclovir exposure were observed. CMV viremia was not detected during prophylaxis. After discontinuing prophylaxis, CMV viremia was seen in 8/36 patients (22%), and 4/36 patients (11%) developed CMV disease. Ganciclovir exposure after administration of valganciclovir 450 mg daily in recipients with GFR ≥60 mL/min was comparable to those previously reported with oral ganciclovir. A routine daily dose of 450 mg valganciclovir appears to be acceptable for CMV prophylaxis in most kidney transplant recipients.

Exposition au VIH, à l'hépatite B et C au cabinet médical et à l'hôpital. Prévention et prophylaxie postexpositionnelle [Exposure to HIV, hepatitis B and C in office practice and hospital. Prevention and post-exposure prophylaxis]

Suite à un accident exposant à du sang (piqûre; coupure), provenant d'un patient infecté, le risque d'infection par VIH est d'environ 0,3% et par le virus de l'hépatite C (VHC) d'environ 0,5%. Chez les personnes vaccinées avec une réponse immunitaire adéquate (titre d'anticorps HBs >100 mUI/ml), aucune infection professionnelle par hépatite B n'a été reconnue en Suisse. La plupart des infections par VIH et VHB peuvent être prévenues par un traitement d'urgence et une prophylaxie postexpositionnelle (PEP). Il n'y a actuellement aucune prophylaxie postexpositionnelle pour le VHC. En cas de transmission de VHC, un traitement rapide par peginterféron et ribavirine est à envisager. Chaque hôpital et cabinet médical doivent mettre sur pied un système pour assurer une prise en charge optimale et en urgence des blessures par piqûres ou coupures. Lors de blessures accidentelles avec du sang de patients séropositifs pour le VIH et dans des situations complexes, il est recommandé de consulter un médecin du personnel ou un infectiologue expérimenté. The risk of infection after an occupational needle stick injury with blood from an infected source patient is approximately 0.3% for HIV and 0.5% for hepatitis C virus (HCV). In Switzerland no cases of occupational HBV infection have been recorded in fully vaccinated persons with a documented adequate vaccine response (HBsantibody titer >100 mIU/mL). Most occupational HIV und HBV infections can be prevented by appropriate emergency measures and post-exposure prophylaxis (PEP). No HCV-PEP is currently available. Early therapy with peginterferon and ribavirin should be considered in cases of occupational HCV seroconversion. Every hospital and office practice should establish a system for 24 h/24 h emergency management of occupational needle stick injuries. In the setting of an HIV-seropositive source patient and in complex situations, early consultation with a specialist in occupational medicine or infectious diseases should be considered.