Minimally Invasive Adrenalectomy: A Population-Based Analysis of Contemporary Trends, Outcomes, Costs, and Impact of Social Determinants of Health.

INTRODUCTION: We sought to analyze temporal trends in the utilization of minimally invasive vs open adrenalectomy in the United States; to assess costs, perioperative outcomes, and the determining factors influencing these variables. METHODS: A retrospective analysis of claims data obtained from PearlDiver Mariner, a Health Insurance Portability and Accountability Act-compliant deidentified nationwide database of insurance billing records, was performed. Per-population utilization rates and trends were analyzed using negative binomial regression and trends tests respectively. Continuous and categorical variables were compared using 2-sided t tests and χ2 tests. Multivariable logistic regression analysis was conducted to identify predictors of perioperative complication. RESULTS: A total of 10,753 patients were identified (mean age 53.3 ± 16.1 years). Using the 2011 to 2014 time frame as reference, utilization of adrenalectomy decreased over time (incidence rate ratio for 2015-2018: 0.65 [95% CI 0.62-0.68, P < .001]; incidence rate ratio for 2019-2021: 0.39 [95% CI 0.37-0.41, P < .001]). Minimally invasive adrenalectomies increased significantly over time (P < .001). A greater number of adrenalectomies were performed by general surgeons compared with urologists (70.4% vs 29.5%). Complications were not significantly predicted by any surgical specialty. Significant predictors for complication rates were Charlson comorbidity index > 1 (odds ratio [OR] 1.11, 95% CI 1.09-1.13), presence of social determinants of health (OR 1.5, 95% CI 1.18-1.88) and open approach (OR 1.54, 95% CI 1.34-1.77). CONCLUSIONS: The number of adrenalectomies in the United States decreased over the past decade, with a shift towards minimally invasive approach. No difference in outcomes for general surgeons vs urologists can be observed. Social determinants of health are independent predictors of increased rate of complications.

Medications Mostly Associated With Ejaculatory Disorders: Assessment of the Eudra-Vigilance and Food and Drug Administration Pharmacovigilance Databases Entries.

OBJECTIVE: To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis. METHODS: The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs. RESULTS: Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01). CONCLUSION: Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.

Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

BACKGROUND: Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. RESULTS: Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). CONCLUSIONS: Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

Prostate Cancer in Transgender Women: Epidemiology, Clinical Characteristics, and Management Challenges.

PURPOSE OF REVIEW: To systematically review the evidence on prostate cancer (PCa) in transgender women (TGW). RECENT FINDINGS: A total of 25 studies were included. Fourteen articles were case reports or case series describing 21 TGW with PCa; 11 papers focused primarily on assessing the incidence or screening of PCa in TGW. The median (range) age of patients with PCa was 63 (45-78) years. Median (range) PSA at diagnosis was 7.5 (0.4-1710) ng/mL. Prostate biopsy detected ISUP 3-5 in 10 (67%) cases. T3-4 stages were described in 7 (64%) patients. Three (14.3%) cases of nodal involvement and 2 (9.5%) of metastases were reported at diagnosis. First-line therapy included radical prostatectomy or radiotherapy ± androgen deprivation therapy in 14 (74 %) subjects. Median (range) follow-up was 24 (2-120) months. A good response to first-line therapy was recorded in 8 (47.1%) cases. Median (range) incidence of PCa in TGW was 44.1 (4.34-140) cases per 100,000 person-years. PCa was significantly less frequent in TGW than in cisgender males (HR 0.4, 95% CI 0.2-0.9). Risk of death after PCa diagnosis was significantly higher in TGW compared to cisgender males (HR 1.91, 95% CI 1.06-3.45). TGW had lower lifetime PSA rates (48% vs. 64.6%, p = 0.048) than cisgender males. Few cases of PCa in TGW are currently reported. PCa seems significantly less frequent in TGW than in cisgender males; however, some data suggest a possible higher mortality in this cohort. TGW appear to have less access to PSA testing than cisgender men.

Exposure considerations in human safety assessment: Report from an EPAA Partners' Forum.

Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are many opportunities to improve and optimise the use of exposure information for chemical safety. The European Partnership for Alternative Approaches to Animal Testing (EPAA) therefore convened a Partners' Forum (PF) to explore exposure considerations in human safety assessment of industrial products to agree key conclusions for the regulatory acceptance of exposure assessment approaches and priority areas for further research investment. The PF recognised the widescale use of exposure information across industrial sectors with the possibilities of creating synergies between different sectors. Further, the PF acknowledged that the EPAA could make a significant contribution to promote the use of exposure data in human safety assessment, with an aim to address specific regulatory needs. To achieve this, research needs, as well as synergies and areas for potential collaboration across sectors, were identified.

Factors Associated with the Acceptance of New Technologies for Ageing in Place by People over 64 Years of Age.

BACKGROUND: In the context of growing population ageing, technologies aimed at helping people age in place play a fundamental role. Acceptance of the implementation of technological solutions can be defined as the intention to use a technology or the effective use of it. Approaches based on the technology acceptance model (TAM) have been shown to have good predictive power for pre-implementation attitudes towards new technologies. OBJECTIVE: To analyze the degree of acceptability of the use of new technologies for ageing in place and the factors associated with greater acceptance in people older than 64 years. METHODOLOGY: A descriptive cross-sectional study was carried out. Sociodemographic, clinical and environmental variables, architectural barriers, social risk and quality of life, degree of autonomy, morbidity, and risk of falls were collected in a population sample over 64 years of age in a large region of western Spain. The degree of acceptance of the use of technologies was measured through a scale based on the TAM. RESULTS: Of the 293 people included in the study, 36.2% exhibited a high acceptability of new technologies, 28.3% exhibited a medium acceptability, and 35.5% exhibited a low acceptability. Of all the factors, age, education level, and living alone were significantly associated with high acceptance in the adjusted analyses. CONCLUSIONS: Younger age, a higher education level, and living alone are factors associated with a greater degree of acceptance of the use of technologies for ageing in place.

An integrated assessment of the Good Environmental Status of Mediterranean Marine Protected Areas.

Local, regional and global targets have been set to halt marine biodiversity loss. Europe has set its own policy targets to achieve Good Environmental Status (GES) of marine ecosystems by implementing the Marine Strategy Framework Directive (MSFD) across member states. We combined an extensive dataset across five Mediterranean ecoregions including 26 Marine Protected Areas (MPAs), their reference unprotected areas, and a no-trawl case study. Our aim was to assess if MPAs reach GES, if their effects are local or can be detected at ecoregion level or up to a Mediterranean scale, and which are the ecosystem components driving GES achievement. This was undertaken by using the analytical tool NEAT (Nested Environmental status Assessment Tool), which allows an integrated assessment of the status of marine systems. We adopted an ecosystem approach by integrating data from several ecosystem components: the seagrass Posidonia oceanica, macroalgae, sea urchins and fish. Thresholds to define the GES were set by dedicated workshops and literature review. In the Western Mediterranean, most MPAs are in good/high status, with P. oceanica and fish driving this result within MPAs. However, GES is achieved only at a local level, and the Mediterranean Sea, as a whole, results in a moderate environmental status. Macroalgal forests are overall in bad condition, confirming their status at risk. The results are significantly affected by the assumption that discrete observations over small spatial scales are representative of the total extension investigated. This calls for large-scale, dedicated assessments to realistically detect environmental status changes under different conditions. Understanding MPAs effectiveness in reaching GES is crucial to assess their role as sentinel observatories of marine systems. MPAs and trawling bans can locally contribute to the attainment of GES and to the fulfillment of the MSFD objectives. Building confidence in setting thresholds between GES and non-GES, investing in long-term monitoring, increasing the spatial extent of sampling areas, rethinking and broadening the scope of complementary tools of protection (e.g., Natura 2000 Sites), are indicated as solutions to ameliorate the status of the basin.

Pre-emptive deceased-donor kidney transplant: A matched cohort study. / Una aproximación al trasplante renal anticipado de donante cadáver. Estudio de cohortes emparejadas.

INTRODUCTION: Currently, kidney transplantation is the treatment of choice for patients with kidney disease who require replacement therapy. Dialysis is a necessary step, but not mandatory prior to transplantation. There is the possibility of pre-emptive transplantation or transplantation in pre-dialysis, that is, without previous dialysis. The aim of the present study is to evaluate the result of our experience with a pre-emptive kidney transplant from a deceased donor. MATERIALS AND METHODS: Retrospective, observational, matched cohort study. We compared 66 pre-emptive with 66 non pre-emptive recipients, who received a first renal graft performed at our centre, matched by age and gender of donors and recipients, time of transplant, immunological risk, immunosuppression and cold ischaemia time. Early graft loss, incidence of acute rejection, delayed graft function, renal function at 12 and 36 months and graft and recipient survival were assessed in this period. RESULTS: The percentage of recipients who presented early graft loss, delayed graft function and acute rejection was similar in both groups. No differences were observed in their renal function at 12 and 36 months after transplantation, as well as the actuarial survival of patients (P=0.801) and grafts (P=0.693) in the studied period. The total calculated cost of the period on dialysis for the control group was 8,033,893.16 euros. CONCLUSIONS: Pre-emptive transplantation can yield comparable outcomes to those for post-dialysis kidney transplantation, and results in better quality of life for patients with end-stage kidney disease, as well as a reduced cost.

Apolipoprotein A-Ib as a biomarker of focal segmental glomerulosclerosis recurrence after kidney transplantation: diagnostic performance and assessment of its prognostic value - a multi-centre cohort study.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) is a serious complication after kidney transplantation. FSGS relapse is suspected by a sudden increase in proteinuria but there is not an accurate noninvasive diagnostic tool to confirm this entity or to detect patients at risk. We aimed to validate the diagnostic performance of ApoA-Ib to detect FSGS relapses by measuring urinary ApoA-Ib in a retrospective cohort of 61 kidney transplanted patients (37 FSGS and 24 non-FSGS). In addition, to assess the ApoA-Ib predictive ability, ApoA-Ib was measured periodically in a prospective cohort of 13 idiopathic FSGS patients who were followed during 1 year after transplantation. ApoA-Ib had a sensitivity of 93.3% and a specificity of 90.9% to diagnose FSGS relapses, with a high negative predictive value (95.2%), confirming our previous results. In the prospective cohort, ApoA-Ib predated the recurrence in four of five episodes observed. In the nonrelapsing group (n = 9), ApoA-Ib was negative in 37 of 38 samples. ApoA-Ib has the potential to be a good diagnostic biomarker of FSGS relapses, providing a confident criterion to exclude false positives even in the presence of high proteinuria. It has also the potential to detect patients at risk of relapse, even before transplantation.

Application of a spatially resolved model to contextualise monitoring data for risk assessment of down-the-drain chemicals over large scales.

Many regulatory screening level exposure assessments are based on simple large scale conceptual scenarios. However, exposure, and therefore risks associated with chemicals, are characterised by high spatial variability. The Scenario assembly tool (ScenAT) is a global screening level model to enable spatially resolved local predictions of environmental concentrations of home and personal care chemicals. It uses the European Union Technical Guidance Document (TGD) equation to predict local scale freshwater concentrations (predicted environmental concentrations - PECs) of chemicals discharged via wastewater. ScenAT uses Geographic Information System (GIS) layers for the underlying socio-economic (population) and environmental parameters (per capita water use, sewage treatment plant connectivity, dilution factor). Using a probabilistic approach, we incorporate sources of uncertainty in the input data (tonnage estimation, removal in sewage treatment plants and seasonal variability in dilution factors) for two case-study chemicals: the antimicrobial triclosan (TCS) and the anionic surfactant linear alkylbenzene sulphonate (LAS). We then compare model estimates of wastewater and freshwater concentrations of TCS and LAS to UK monitoring data. Comparison showed that modeled PECs were on average higher than mean measured data for TCS and LAS by a factor 1.8 and 1.4, respectively. Considering the uncertainty associated with both model and monitoring data, the use of a probabilistic approach using the ScenAT model for screening assessment is reasonable. The combination of modelled and monitoring data enables the contextualisation of monitoring data. Spatial PECs can be used to identify areas of elevated concentration for further refined assessment.

Enhancing fish Underwater Visual Census to move forward assessment of fish assemblages: An application in three Mediterranean Marine Protected Areas.

Monitoring fish assemblages is needed to assess whether Marine Protected Areas (MPAs) are meeting their conservation and fisheries management goals, as it allows one to track the progress of recovery of exploited species and associated communities. Underwater Visual Census techniques (UVC) are used to monitor fish assemblages in MPAs. UVCs should be adapted to fish abundance, body-size and behaviour, which can strongly affect fish detectability. In Mediterranean subtidal habitats, however, UVC strip transects of one surface area (25x5 m2) are commonly used to survey the whole fish assemblage, from large shy fish to small crypto-benthic fish. Most high trophic level predators (HTLPs) are large shy fish which rarely swim close to divers and, consequently, their abundance may be under-estimated with commonly used transects. Here, we propose an improvement to traditional transect surveys to better account for differences in behaviour among and within species. First, we compared the effectiveness of combining two transect surface areas (large: 35x20 m2; medium: 25x5 m2) in quantifying large, shy fish within and outside Mediterranean MPAs. We identified species-specific body-size thresholds defining a smaller and a larger size class better sampled by medium and large transects respectively. Combining large and medium transects provided more accurate biomass and species richness estimates for large, shy species than using medium transects alone. We thus combined the new approach with two other transect surface areas commonly used to survey crypto-benthic (10x1 m2) and necto-benthic (25x5 m2) species in order to assess how effectively MPAs protection the whole fish assemblage. We verified that MPAs offer significant protection for HTLPs, their response in terms of biomass and density increase in MPAs was always higher in magnitude than other functional groups. Inside MPAs, the contribution of HTLP reached >25% of total fish biomass, against < 2% outside MPAs. Surveys with multiple transect surface areas allow for a more realistic assessment of the structure of the whole fish assemblage and better assessment of potential recovery of HTLPs within reserves of HTLP.

Toward refined environmental scenarios for ecological risk assessment of down-the-drain chemicals in freshwater environments.

Current regulatory practice for chemical risk assessment suffers from the lack of realism in conventional frameworks. Despite significant advances in exposure and ecological effect modeling, the implementation of novel approaches as high-tier options for prospective regulatory risk assessment remains limited, particularly among general chemicals such as down-the-drain ingredients. While reviewing the current state of the art in environmental exposure and ecological effect modeling, we propose a scenario-based framework that enables a better integration of exposure and effect assessments in a tiered approach. Global- to catchment-scale spatially explicit exposure models can be used to identify areas of higher exposure and to generate ecologically relevant exposure information for input into effect models. Numerous examples of mechanistic ecological effect models demonstrate that it is technically feasible to extrapolate from individual-level effects to effects at higher levels of biological organization and from laboratory to environmental conditions. However, the data required to parameterize effect models that can embrace the complexity of ecosystems are large and require a targeted approach. Experimental efforts should, therefore, focus on vulnerable species and/or traits and ecological conditions of relevance. We outline key research needs to address the challenges that currently hinder the practical application of advanced model-based approaches to risk assessment of down-the-drain chemicals. Integr Environ Assess Manag 2017;13:233-248. © 2016 SETAC.

Five key attributes can increase marine protected areas performance for small-scale fisheries management.

Marine protected areas (MPAs) have largely proven to be effective tools for conserving marine ecosystem, while socio-economic benefits generated by MPAs to fisheries are still under debate. Many MPAs embed a no-take zone, aiming to preserve natural populations and ecosystems, within a buffer zone where potentially sustainable activities are allowed. Small-scale fisheries (SSF) within buffer zones can be highly beneficial by promoting local socio-economies. However, guidelines to successfully manage SSFs within MPAs, ensuring both conservation and fisheries goals, and reaching a win-win scenario, are largely unavailable. From the peer-reviewed literature, grey-literature and interviews, we assembled a unique database of ecological, social and economic attributes of SSF in 25 Mediterranean MPAs. Using random forest with Boruta algorithm we identified a set of attributes determining successful SSFs management within MPAs. We show that fish stocks are healthier, fishermen incomes are higher and the social acceptance of management practices is fostered if five attributes are present (i.e. high MPA enforcement, presence of a management plan, fishermen engagement in MPA management, fishermen representative in the MPA board, and promotion of sustainable fishing). These findings are pivotal to Mediterranean coastal communities so they can achieve conservation goals while allowing for profitable exploitation of fisheries resources.

Food web modeling of a river ecosystem for risk assessment of down-the-drain chemicals: a case study with AQUATOX.

Conventional approaches to estimating protective ecotoxicological thresholds of chemicals, i.e. predicted no-effect concentrations (PNEC), for an entire ecosystem are based on the use of assessment factors to extrapolate from single-species toxicity data derived in the laboratory to community-level effects on ecosystems. Aquatic food web models may be a useful tool to improve the ecological realism of chemical risk assessment because they enable a more insightful evaluation of the fate and effects of chemicals in dynamic trophic networks. A case study was developed in AQUATOX to simulate the effects of the anionic surfactant linear alkylbenzene sulfonate and the antimicrobial triclosan on a lowland riverine ecosystem. The model was built for a section of the River Thames (UK), for which detailed ecological surveys were available, allowing for a quantification of energy flows through the whole ecosystem. A control scenario was successfully calibrated for a simulation period of one year, and tested for stability over six years. Then, the model ecosystem was perturbed with varying inputs of the two chemicals. Simulations showed that both chemicals rapidly approach steady-state, with internal concentrations in line with the input bioconcentration factors throughout the year. At realistic environmental concentrations, both chemicals have insignificant effects on biomass trends. At hypothetical higher concentrations, direct and indirect effects of chemicals on the ecosystem dynamics emerged from the simulations. Indirect effects due to competition for food sources and predation can lead to responses in biomass density of the same magnitude as those caused by direct toxicity. Indirect effects can both exacerbate or compensate for direct toxicity. Uncertainties in key model assumptions are high as the validation of perturbed simulations remains extremely challenging. Nevertheless, the study is a step towards the development of realistic ecological scenarios and their potential use in prospective risk assessment of down-the-drain chemicals.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH.

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool.

Large-scale assessment of Mediterranean marine protected areas effects on fish assemblages.

Marine protected areas (MPAs) were acknowledged globally as effective tools to mitigate the threats to oceans caused by fishing. Several studies assessed the effectiveness of individual MPAs in protecting fish assemblages, but regional assessments of multiple MPAs are scarce. Moreover, empirical evidence on the role of MPAs in contrasting the propagation of non-indigenous-species (NIS) and thermophilic species (ThS) is missing. We simultaneously investigated here the role of MPAs in reversing the effects of overfishing and in limiting the spread of NIS and ThS. The Mediterranean Sea was selected as study area as it is a region where 1) MPAs are numerous, 2) fishing has affected species and ecosystems, and 3) the arrival of NIS and the northward expansion of ThS took place. Fish surveys were done in well-enforced no-take MPAs (HP), partially-protected MPAs (IP) and fished areas (F) at 30 locations across the Mediterranean. Significantly higher fish biomass was found in HP compared to IP MPAs and F. Along a recovery trajectory from F to HP MPAs, IP were similar to F, showing that just well enforced MPAs triggers an effective recovery. Within HP MPAs, trophic structure of fish assemblages resembled a top-heavy biomass pyramid. Although the functional structure of fish assemblages was consistent among HP MPAs, species driving the recovery in HP MPAs differed among locations: this suggests that the recovery trajectories in HP MPAs are likely to be functionally similar (i.e., represented by predictable changes in trophic groups, especially fish predators), but the specific composition of the resulting assemblages may depend on local conditions. Our study did not show any effect of MPAs on NIS and ThS. These results may help provide more robust expectations, at proper regional scale, about the effects of new MPAs that may be established in the Mediterranean Sea and other ecoregions worldwide.

Evolution of the sewage treatment plant model SimpleTreat: use of realistic biodegradability tests in probabilistic model simulations.

Given the large number of chemicals under regulatory scrutiny, models play a crucial role in the screening phase of the environmental risk assessment. The sewage treatment plant (STP) model SimpleTreat 3.1 is routinely applied as part of the European Union System for the Evaluation of Substances to estimate the fate and elimination of organic chemicals discharged via sewage. SimpleTreat estimates tend to be conservative and therefore only useful for lower-tier assessments. A probabilistic version of SimpleTreat was built on the updated version of the model (SimpleTreat 3.2, presented in a parallel article in this issue), embracing likeliest as well as worst-case conditions in a statistically robust way. Probabilistic parameters representing the variability of sewage characteristics, STP design, and operational parameters were based on actual STP conditions for activated sludge plants in Europe. An evaluation study was carried out for 4 chemicals with distinct sorption and biodegradability profiles: tonalide, triclosan, trimethoprim, and linear alkylbenzene sulfonate. Simulations incorporated information on biodegradability simulation studies with activated sludge (OECD 314B and OECD 303A tests). Good agreement for both median values and variability ranges was observed between model estimates and monitoring data. The uncertainty analysis highlighted the importance of refined data on partitioning and biodegradability in activated sludge to achieve realistic estimates. The study indicates that the best strategy to refine the exposure assessment of down-the-drain chemicals is by integrating higher-tier laboratory data with probabilistic STP simulations and, if possible, by comparing them with monitoring data for validation.

[Long-term prognosis in diabetic patients in whom revascularization is deferred following fractional flow reserve assessment]. / Pronóstico a largo plazo de diferir la intervención coronaria en diabéticos sobre la base de la reserva fraccional de flujo.

INTRODUCTION AND OBJECTIVES: The fractional flow reserve (FFR) has been shown to be a valid and useful measure in the functional assessment of coronary stenoses of intermediate severity. Our aim was to determine the usefulness of FFR assessment in diabetic patients, in whom determination of the FFR can be influenced by microvascular dysfunction. METHODS: Between 1997-2004, FFR assessment was used to evaluate 222 consecutive coronary lesions judged by an interventional cardiologist to be of intermediate severity (ie, 40%-70%). Intravenous adenosine (140 microg/kg per min) was used to achieve maximum hyperemia. The occurrence of cardiac events (ie, death, non-fatal acute myocardial infarction, and target lesion revascularization) was compared in diabetics and nondiabetics in whom FFR assessment gave a negative result and intervention was deferred. The mean follow-up period was 30+/-21 months. RESULTS: Revascularization was deferred for 144 lesions (in 136 patients) in which the FFR was >/=0.75. Of these, 42 lesions (29.2%) were in diabetics (40 patients). The proportion of patients who were female or who had hypertension, dyslipidemia or multivessel disease was greater in the diabetic group. There was no difference in indications for coronary angiography. In both groups, the most frequently investigated vessel was the left anterior descending coronary artery. The mean FFR was 0.87+/-0.06, and there was no difference between the groups. On long-term follow-up, there was no difference in the rate of death or acute myocardial infarction. Overall, 8.8% of nondiabetics and 14.3% of diabetics with a negative FFR test result required target lesion revascularization (P=.32). CONCLUSIONS: Our results indicate that deferring percutaneous coronary intervention in diabetics with a moderately severe coronary artery stenosis and an FFR >/=0.75 is safe.

O papel do Governo, dos trabalhadores e da socidade civil no controle da insalubridade dentro e fora da fábrica na Inglaterra / The role of the Government, workers and society concerning the control of insalubrity inside and outside of plants in England

A Inglaterra foi um dos primeiros países do mundo a se industrializar. Tem uma larga experiência com problemas com problemas de segurança e saúde dos trabalhadores na linha de produçäo e também com a saúde da populaçäo e a preservaçäo do meio ambiente. É, portanto, de grande importância para nós brasileiros conhecemos essa experiência. Por isso solicitamos uma bolsa de estudos a Fundaçäo de Amparo a Pesquisa do Estado de Säo Paulo - FAFESP, junrto ao TUC - "INSTITUTE OF Occupational Helth of the London School of Hygiene and Tropical Medicine". Durante o ano de nossa estada em Londres procuramos compreender as responsabilidades das organizaçöes governamentais e o poder de influência dos Sindicatos e de organizaçöes civis nas tomadas de decisäo e na execuçäo da política de controle de poluiçäo ambiental em geral e de insalubridade dentro das fábricas, naquele país. Este trabalho representa nosso ponto de vista pessoal sobre o asssunto e é apresentado como contribuiçäo a todos aqueles que trabalham nessa área no Brasil