Bioavailability of pharmaceuticals in waters close to wastewater treatment plants: use of fish bile for exposure assessment

Pharmaceuticals are ubiquitous in surface waters as a consequence of discharges from municipal wastewater treatment plants. However, few studies have assessed the bioavailability of pharmaceuticals to fish in natural waters. In the present study, passive samplers and rainbow trout were experimentally deployed next to three municipal wastewater treatment plants in Finland to evaluate the degree of animal exposure. Pharmaceuticals from several therapeutic classes (in total 15) were analyzed by liquid chromatography-tandem mass spectrometry in extracts of passive samplers and in bile and blood plasma of rainbow trout held at polluted sites for 10 d. Each approach indicated the highest exposure near wastewater treatment plant A and the lowest near that of plant C. Diclofenac, naproxen, and ibuprofen were found in rainbow trout, and their concentrations in bile were 10 to 400 times higher than in plasma. The phase I metabolite hydroxydiclofenac was also detected in bile. Hence, bile proved to be an excellent sample matrix for the exposure assessment of fish. Most of the monitored pharmaceuticals were found in passive samplers, implying that they may overestimate the actual exposure of fish in receiving waters. Two biomarkers, hepatic vitellogenin and cytochrome P4501A, did not reveal clear effects on fish, although a small induction of vitellogenin mRNA was observed in trout caged near wastewater treatment plants B and C.

Position paper on diagnosis and treatment of atopic dermatitis

The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease.

Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced spinal osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increase bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparthyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss to reduce vertebral fracture risk. Calcitonin may be of interest in situation where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be manage. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification

BACKGROUND: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs). METHODS: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs. RESULTS: Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate. CONCLUSIONS: The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: a prospective cohort study

Objective. To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public sector treatment facilities in the Free State province, South Africa. Design. Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007, and assessed percentage initiating ART and percentage dead at 1 year after enrolment. Multivariable logistic regression was used to estimate associations of facility-level and patient-level characteristics with both mortality and treatment status. Results. Of 44 866 patients enrolled, 15 219 initiated treatment within 1 year; 8 778 died within 1 year, 7 286 before accessing ART. Outcomes at 1 year varied greatly across facilities and more variability was explained by facility-level factors than by patient-level factors. The odds of starting treatment within 1 year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at 1 year compared with those enrolled in facilities that did not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count ≤50 cells/μl), or underweight (<50 kg). Men were also more likely to die in the first year after enrolment. Conclusions. Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access, especially for men.

EAU guidelines on surgical treatment of urinary incontinence

The European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology. OBJECTIVE: We present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY: The full version of the guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report. CONCLUSIONS: These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where high-level evidence is lacking, they present a consensus of expert panel opinion.

Effects of oligotrophication on primary production in peri-alpine lakes

During the second half of the 20th century untreated sewage released from housing and industry into natural waters led to a degradation of many freshwater lakes and reservoirs worldwide. In order to mitigate eutrophication, wastewater treatment plants, including Fe-induced phosphorus precipitation, were implemented throughout the industrialized world, leading to reoligotrophication in many freshwater lakes. To understand and assess the effects of reoligotrophication on primary productivity, we analyzed 28 years of 14C assimilation rates, as well as other biotic and abiotic parameters, such as global radiation, nutrient concentrations and plankton densities in peri-alpine Lake Lucerne, Switzerland. Using a simple productivity-light relationship, we estimated continuous primary production and discussed the relation between productivity and observed limnological parameters. Furthermore, we assessed the uncertainty of our modeling approach based on monthly 14C assimilation measurements using Monte Carlo simulations. Results confirm that monthly sampling of productivity is sufficient for identifying long-term trends in productivity and that conservation management has successfully improved water quality during the past three decades via reducing nutrients and primary production in the lake. However, even though nutrient concentrations have remained constant in recent years, annual primary production varies significantly from year to year. Despite the fact that nutrient concentrations have decreased by more than an order of magnitude, primary production has decreased only slightly. These results suggest that primary production correlates well to nutrients availability but meteorological conditions lead to interannual variability regardless of the trophic status of the lake. Accordingly, in oligotrophic freshwaters meteorological forcing may reduce productivity impacting on the entire food chain of the ecosystem.

EAU guidelines on surgical treatment of urinary incontinence

CONTEXT The European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology. OBJECTIVE We present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience. EVIDENCE ACQUISITION Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY The full version of the guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report. CONCLUSIONS These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where high-level evidence is lacking, they present a consensus of expert panel opinion.

Into the abyss of Lake Geneva: the elemo interdisciplinary field investigation using the MIR submersibles

In summer 2011, the two Russian MIR sub- mersibles were brought to Switzerland to perform deep water dives in Lake Geneva. Research teams from several environmental science institutes, both national and inter- national, participated in this interdisciplinary effort to investigate the deeper parts of Lake Geneva. Using the MIRs allowed the scientists to see and precisely select the sites where they could extract specific sediment cores and carry out detailed in situ measurements at the sediment– water boundary. One focus site was the surrounding of the outlet of the wastewater treatment plant of the City of Lausanne, which discharges into the Vidy Bay. The investigations concentrated on the pollution of the local sediments, pollution-related ecotoxicological risks, micro- bial activity and spreading and removal of the effluents from the bay to the open waters of the lake. The other focus site was the Rhoˆne River delta and its subaquatic canyons, which formed as a result of the long-term interplay of the deposition of river-borne sediments and flood-triggered canyon erosion events.

Sustainable Wastewater Management: Is it Possible to Regulate Micropollution in the Future by Learning from the Past? A Policy Analysis

This paper applies a policy analysis approach to the question of how to effectively regulate micropollution in a sustainable manner. Micropollution is a complex policy problem characterized by a huge number and diversity of chemical substances, as well as various entry paths into the aquatic environment. It challenges traditional water quality management by calling for new technologies in wastewater treatment and behavioral changes in industry, agriculture and civil society. In light of such challenges, the question arises as to how to regulate such a complex phenomenon to ensure water quality is maintained in the future? What can we learn from past experiences in water quality regulation? To answer these questions, policy analysis strongly focuses on the design and choice of policy instruments and the mix of such measures. In this paper, we review instruments commonly used in past water quality regulation. We evaluate their ability to respond to the characteristics of a more recent water quality problem, i.e., micropollution, in a sustainable way. This way, we develop a new framework that integrates both the problem dimension (i.e., causes and effects of a problem) as well as the sustainability dimension (e.g., long-term, cross-sectoral and multi-level) to assess which policy instruments are best suited to regulate micropollution. We thus conclude that sustainability criteria help to identify an appropriate instrument mix of end-of-pipe and source-directed measures to reduce aquatic micropollution.