Mediterranean springs: Keystone ecosystems and biodiversity refugia threatened by global change.

Mediterranean spring ecosystems are unique habitats at the interface between surface water and groundwater. These ecosystems support a remarkable array of biodiversity and provide important ecological functions and ecosystem services. Spring ecosystems are influenced by abiotic, biotic, and anthropogenic factors such as the lithology of their draining aquifers, their climate, and the land use of their recharge area, all of which affect the water chemistry of the aquifer and the spring discharges. One of the most relevant characteristics of spring ecosystems is the temporal stability of environmental conditions, including physicochemical features of the spring water, across seasons and years. This stability allows a wide range of species to benefit from these ecosystems (particularly during dry periods), fostering an unusually high number of endemic species. However, global change poses important threats to these freshwater ecosystems. Changes in temperature, evapotranspiration, and precipitation patterns can alter the water balance and chemistry of spring water. Eutrophication due to agricultural practices and emergent pollutants, such as pharmaceuticals, personal care products, and pesticides, is also a growing concern for the preservation of spring biodiversity. Here, we provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems. We then describe their ecological value and biodiversity patterns and highlight the main risks these ecosystems face. Moreover, we identify existing knowledge gaps to guide future research in order to fully uncover the hidden biodiversity within these habitats and understand the main drivers that govern them. Finally, we provide a brief summary of recommended actions that should be taken to effectively manage and preserve Mediterranean spring ecosystems for future generations. Even though studies on Mediterranean spring ecosystems are still scarce, our review shows there are sufficient data to conclude that their future viability as functional ecosystems is under severe threat.

Modelling the seasonal impacts of a wastewater treatment plant on water quality in a Mediterranean stream using microbial indicators.

Faecal pollution modelling is a valuable tool to evaluate and improve water management strategies, especially in a context of water scarcity. The reduction dynamics of five faecal indicator organisms (E. coli, spores of sulphite-reducing clostridia, somatic coliphages, GA17 bacteriophages and a human-specific Bifidobacterium molecular marker) were assessed in an intermittent Mediterranean stream affected by a wastewater treatment plant (WWTP). Using Bayesian inverse modelling, the decay rates of each indicator were correlated with two environmental drivers (temperature and streamflow downstream of the WWTP) and the generated model was used to evaluate the self-depuration distance (SDD) of the stream. A consistent increase of 1-2 log10 in the concentration of all indicators was detected after the discharge of the WWTP effluent. The decay rates showed seasonal variation, reaching a maximum in the dry season, when SDDs were also shorter and the stream had a higher capacity to self-depurate. High seasonality was observed for all faecal indicators except for the spores of sulphite-reducing clostridia. The maximum SDD ranged from 3 km for the spores of sulphite-reducing clostridia during the dry season and 15 km for the human-specific Bifidobacterium molecular marker during the wet season. The SDD provides a single standardized metric that integrates and compares different contamination indicators. It could be extended to other Mediterranean drainage basins and has the potential to integrate changes in land use and catchment water balance, a feature that will be especially useful in the transient climate conditions expected in the coming years.

Nitrate pollution reduces bryophyte diversity in Mediterranean springs.

Anthropogenic activities and intensive farming are causing nitrate pollution in groundwater bodies. These aquifers are drained by springs which, in the Mediterranean region, act as refugia for preserving biodiversity of species that need continuous water. Some springs are also used for drinking water for wild animals, livestock and humans, so if their water quality is compromised it can become a threat to public health. However, the impact of nitrate pollution on these biotic communities remains unknown. We sampled 338 assemblages of aquatic and semi-aquatic bryophytes (i.e., hygrophytic mosses and liverworts) growing in springs in a gradient of water conductivity, nitrate concentration and climate and distributed across the north-east of the Iberian Peninsula to investigate the impact of nitrate pollution on the diversity of bryophytes and moss functional traits in Mediterranean springs. Based on previous literature suggesting that increased nitrogen load decreases biodiversity in grasslands and freshwater ecosystems, we hypothesised that water nitrate pollution in springs decreases bryophyte diversity at the local and regional scales. Our results indicated that, at the local scale (spring), nitrate pollution reduced the number and the likelihood of finding a rare species in springs. Rare species were found in 4% of the springs with nitrate above 50 mg L-1 but in 32% of the springs with nitrate below 50 mg L-1. Moss, liverwort and overall bryophyte diversity were not directly affected by nitrate at the local scale but nitrate consistently decreased diversity of mosses, liverworts and rare bryophyte species at the regional scale. We also found that warmer and drier springs presented fewer bryophyte species. Our results show that the combination of nitrate pollution, increasing temperature and drought could severely threaten bryophyte diversity in Mediterranean springs. Our results indicate that the absence of rare bryophytes could be used as a bioindicator of nitrate pollution in springs.

Trial-based cost-effectiveness of abatacept for rheumatoid arthritis patients in Italy.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, inflammatory disorder leading to disability and reduced quality of life. Effective treatment is a significant economic burden on the Italian healthcare system. Economic models in RA are commonly based on indirect treatment comparisons. METHODS: This study assessed the cost-effectiveness of abatacept relative to adalimumab for RA in Italy based on a head-to-head trial by means of a cost-consequence analysis. RESULTS: Health benefits based on the most stringent efficacy criteria were in favor of abatacept compared to adalimumab. Rates for more costly adverse events were higher for adalimumab compared to abatacept, which was reflected in the lower costs for abatacept (-€237,246 or -€237per patient). CONCLUSION: The health economic value of abatacept compared with adalimumab from the perspective of the Italian NHS depends on the choice of health outcome. Health gains with abatacept were generally based on more stringent criteria and lower total costs.

Methods applied in cost-effectiveness models for treatment strategies in type 2 diabetes mellitus and their use in Health Technology Assessments: a systematic review of the literature from 2008 to 2013.

OBJECTIVE: To identify and compare health-economic models that were developed to evaluate the cost-effectiveness of treatments for type 2 diabetes mellitus (T2DM), and their use within Health Technology Assessments (HTAs). METHODS: In total, six commonly used databases were searched for articles published between October 2008 and January 2013, using a protocolized search strategy and inclusion criteria. The websites of HTA organizations in nine countries, and proceedings from five relevant conferences, were also reviewed. The identified new health-economic models were qualitatively assessed using six criteria that were developed based on technical components, and characteristics related to the disease or the treatments being assessed. Finally, the number of times the models were applied within HTA reports, published literature, and/or major conferences was determined. RESULTS: Thirteen new models were identified and reviewed in depth. Most of these were based on identical key data sources, and applied a similar model structure, either using Markov modeling or microsimulation techniques. The UKPDS equations and panel regressions were frequently used to estimate the occurrence of diabetes-related complications and the probability of developing risk factors in the long term. The qualitative assessment demonstrated that the CARDIFF, Sheffield T2DM and ECHO T2DM models seem technically equipped to appropriately assess the long-term health-economic consequences of chronic treatments for patients with T2DM. It was observed that the CORE model is the most widely described in literature and conferences, and the most often applied model within HTA submissions, followed by the CARDIFF and UKPDS models. CONCLUSION: This research provides an overview of T2DM models that were developed between 2008 and January 2013. The outcomes of the qualitative assessments, combined with frequent use in local reimbursement decisions, prove the applicability of the CORE, CARDIFF and UKPDS models to address decision problems related to the long-term clinical and economic consequences of new and existing T2DM treatments.

Ciprofloxacin plus fluocinolone acetonide versus ciprofloxacin alone in the treatment of diffuse otitis externa.

OBJECTIVE: We aimed to evaluate the clinical efficacy of ciprofloxacin plus fluocinolone acetonide (antibiotic plus corticosteroid) ear drops compared to ciprofloxacin (antibiotic) ear drops in diffuse otitis externa. METHODS: This was a multicentre, randomised, parallel-group, double-blind study involving 590 patients of both sexes aged 7 years or older. RESULTS: The rate of clinical cure was higher (p = 0.01) with ciprofloxacin plus fluocinolone acetonide than with ciprofloxacin alone. The mean total symptom score was lower with ciprofloxacin plus fluocinolone acetonide (p = 0.005). No differences were found in the percentage of patients reporting resolution of otalgia between patients receiving ciprofloxacin plus fluocinolone acetonide and patients receiving only ciprofloxacin. Resolution of oedema and otorrhoea (p = 0.003 and p = 0.002, respectively) was higher with ciprofloxacin plus fluocinolone acetonide, as was eradication or presumed eradication (p = 0.003). There were eight mild adverse events, three with the ciprofloxacin plus fluocinolone acetonide combination (not related to the treatment) and five when ciprofloxacin was administered alone (directly related to the treatment). CONCLUSIONS: Ciprofloxacin plus fluocinolone acetonide is a more effective treatment for diffuse otitis externa than ciprofloxacin alone. The ciprofloxacin plus fluocinolone acetonide combination also has an excellent safety profile.

Economic evaluation of posaconazole vs fluconazole in the prevention of invasive fungal infections in patients with GVHD following haematopoietic SCT.

Posaconazole has been proven to be as effective as fluconazole in the prevention of invasive fungal infections (IFI) in allogeneic haematopoietic SCT patients with GVHD. We assessed, from the perspective of the Spanish National Health Service, the cost-effectiveness of posaconazole vs fluconazole in preventing IFI. A decision-analytic model was developed to assess the average per patient treatment costs, IFIs avoided, life-years gained (LYG) and incremental cost per LYG for each prophylactic treatment used (in euros at 2007 prices). Patients are assumed to have received either posaconazole or fluconazole. The probabilities of IFI, IFI-related death and death from other causes were obtained from a single clinical trial. Long-term mortality and costs were estimated from secondary sources. Posaconazole was associated with fewer IFIs (5.3 vs 9%), increased LYG (8.01 vs 7.78) and higher IFI-related costs ([euro]11 585 vs [euro]6 959) per patient compared with fluconazole. The incremental cost-effectiveness of posaconazole vs fluconazole was estimated at [euro]20 246 per LYG. There was a 70% probability that posaconazole is cost-effective at a [euro]30 000 per LYG threshold. In conclusion, compared with fluconazole, posaconazole prophylaxis is a cost-effective strategy for the prevention of IFI in patients with GVHD.

Prognostic significance of surgical margins in transoral CO2 laser microsurgery for T1-T4 pharyngo-laryngeal cancers.

Histological affected or close margin is an adverse factor in conventional surgery of larynx-hypopharynx cancer. Our objective was to analyze the relevance of the margins in transoral laser microsurgery (TLM). A retrospective study of 357 consecutive patients with cancer of the larynx and hypopharynx (T1-T4) treated with TLM. Three possible margins were considered: tumor free, affected, and uncertain. An affected margin showed marked tumor infiltration. An uncertain margin was defined when the sample was insufficient, when it showed carbonization impeding accurate evaluation, or when tumor cells were less than 2 mm. Margins were free in 254 (71.1%) patients, affected in 64 (17.9%) and uncertain in 39 (10.9%). One hundred and three patients (28.9%) presented tumor relapse. The margins were associated with tumor relapse (P < 0.001), but were not significantly related to the tumor site (P = 0.307), the pT classification (P = 0.183), or the difficulty of surgical exposure (P = 0.427). Distant metastases were found in 4.7% of the patients with free margins, in 7.7% of those with uncertain margins, and in 14.1% with affected margins. These differences were statistically significant (P = 0.028). Tumor involvement of the surgical margin was associated with higher rates of local relapse, distant metastasis and the necessity of salvage surgery, together with a lower specific actuarial survival rate.

Leaf litter dynamics and nitrous oxide emission in a Mediterranean riparian forest: implications for soil nitrogen dynamics.

Mediterranean riparian zones can experience severe drought periods that lead to low soil moisture content, which dramatically affects their performance as nitrate removal systems. In the Mediterranean riparian zone of this study, we determined that N2O emission was practically nil. To understand the role of forest floor processes in nitrogen retention of a Mediterranean riparian area, we studied leaf litter dynamics of two tree species, London planetree [Platanus x acerifolia (Aiton) Willd.] and alder [Alnus glutinosa (L.) Gaertn.], for two years, along with soil nitrogen mineralization rates. Annual leaf litter fall equaled 562.6 +/- 10.1 (standard error) g dry wt. m(-2), 68% of which was planetree and 32% of which was alder. The temporal distribution of litterfall showed a two-peak annual cycle, one occurring in midsummer, the other in autumn. Planetree provided the major input of organic nitrogen to the forest floor, and the amount of planetree leaves remaining on the forest floor was equivalent to approximately four years of stock. Leaf litter decomposition was three times higher for alder (decay coefficient [k] = 1.13 yr(-1)) than for planetree (k = 0.365 yr(-1)). Mineralization rates showed a seasonal pattern, with the maximum rate in summer (1.92 mg N kg(-1) d(-1)). Although the forest floor was an important sink for nitrogen due to planetree leaf accumulation, 7.5% of this leaf litter was scoured to the streambed by wind. This loss was irrelevant for alder leaves. Due to the litter quality, the forest floor of this Mediterranean riparian forest acts as a nitrogen sink.

[Determination of plasma ciprofloxacin levels in children treated with 0.2% topical ciprofloxacin for tympanic perforation]. / Determinación de niveles plasmáticos de ciprofloxacino en niños tratados con ciprofloxacino tópico al 0,2% en presencia de perforación timpánica.

Topical drug use can produce locally adverse effects by direct action or systemic effects as a result of drug absorption. Local tolerance of topically-administered ciprofloxacin (ear drops) and serum antibiotic levels after 7-10 days of treatment were evaluated in 30 children with tympanic membrane perforation and suppuration. There were no signs of local intolerance or ototoxicity and significant serum ciprofloxacin levels were not detected. We conclude that ciprofloxacin ear drops can be safely used in children with suppurative otitis media and tympanic perforation.

Determinación de niveles plasmáticos de ciprofloxacino en niños tratados con ciprofloxacino tópico al 0,2 por ciento en presencia de perforación timpánica / Determination of plasma ciprofloxacin levels in children treated with 0.2 por ciento topical ciprofloxacin for tympanic perforation

La administración de un fármaco, por vía tópica puede producir efectos secundarios a nivel local por la propia acción del fármaco o a nivel sistémico como consecuencia de la absorción del mismo. En el presente estudio, realizado en una población infantil en presencia de una perforación timpánica, se determinan la tolerancia local de ciprofloxacino cuando se administra por vía tópica ótica y los niveles plasmáticos del mismo después de un tratamiento tópico ótico de 7-10 días de duración. En ninguno de los 30 casos estudiados se presentó intolerancia local ni signos de ototoxicidad ni se determinaron niveles significativos de ciprofloxacino en plasma (AU)

Topical drug use can produce locally adverse effects by direct action or systemic effects as a result of drug absorption. Local tolerance of topically-administered ciprofloxacin (ear drops) and serum antibiotic levels after 7-10 days of treatment were evaluated in 30 children with tympanic membrane perforation and suppuration. There were no signs of local intolerance or ototoxicity and significant serum ciprofloxacin levels were not detected. We conclude that ciprofloxacin ear drops can be safely used in children with suppurative otitis media and tympanic perforation (AU)

Algal biomass in a disturbed Atlantic river: water quality relationships and environmental implications.

Benthic algal biomass was determined at 38 sites along the Oria, a river with intense human activity on its watershed. Water temperature, total suspended solids and nutrient concentration affected algal biomass in different ways. Lower values of algal biomass [(chlorophyll-a concentration and ash-free dry weight (AFDW)] were found in the headwaters and forested tributaries, but also at sites receiving high deposition of solids (due to the outflow from paper mills and quarries). Higher values of algal biomass (both chlorophyll-a and AFDW) were common both in the main stretch of the river and in some tributaries receiving urban sewage outflows. Averages and ranges of temperature and dissolved oxygen concentration were compared for two continuously monitored stations. One of them (forested, nutrient-poor) had low algal biomass, while the second (open, nutrient-rich) showed high chlorophyll-a concentration. Accumulation of algal biomass had environmental implications both in water quality and in the fish diversity of the Oria. Diel variations of dissolved oxygen were much higher (and reached hypoxia) at the site with higher biomass accumulation. The abundance of a fish community (dominated by cyprinids) more tolerant to hypoxia at that site can partly be attributed to the influence of algal biomass accumulation.

[Prospective double-blind randomized study of the efficacy and tolerance of topical ciprofloxacin vs topical gentamicin in the treatment of simple chronic otitis media and diffuse external otitis]. / Estudio prospectivo doble-ciego randomizado de la eficacia y tolerancia de ciprofloxacino tópico versus gentamicina tópica en el tratamiento de la otitis media crónica supurada simple y de la otitis externa difusa.

A prospective, randomized double-blind study was made of topical ciprofloxacillin (0.5%) compared with topical gentamicin (0.3%) in the treatment of simple chronic otitis media (COM) and diffuse external otitis (DEO). The study included 47 patients with COM and 54 patients with DEO. Success rates in the COM subgroup were 95% for ciprofloxacillin and 96% for gentamicin (p = 0.082), and in the DEO subgroup, 87% for ciprofloxacillin and 79% for gentamicin (p = 0.19). Both drugs were well tolerated and there was no significant change in audiometric measurements with either medication in either group. Therefore, ciprofloxacillin is at least as effective as gentamicin in such ear infections and has no potential ototoxic effect.

[Yag-laser for the treatment of laryngeal and oral hemangiomas]. / Yag-Láser en el tratamiento de hemangiomas de laringe y ca vidad oral.

Laryngeal and bucal hemangiomas are uncommon, although they carry with them, because of its sitting, a vital risk. The AA. report 2 hemangioma cases, one localized on the edge of the tongue, the other one on the aryepiglottic fold. Both were treated with photocoagulation by neodymiun-yttrium-aluminium (Nd-YaG) laser, with favorable follow-up and few complications.

Effect of ethylene on naringin, narirutin and nootkatone accumulation in grapefruit.

This paper studies the effect of different concentrations of ethephon on the levels of the sesquiterpene, nootkatone, and of the flavanones, naringin and narirutin, in grapefruit fruits. The results show that nootkatone synthesis and/or accumulation was stimulated by all the concentrations of ethephon assayed, while the levels of naringin and narirutin in the rind diminished. These results open up new perspectives concerning the possible regulation of the secondary metabolism of the plants.

Accumulation of hexachlorobenzene in humans: a long standing risk.

1. Hexachlorobenzene (HCB) internal dose in the general population of Barcelona (Spain) was estimated after new indications of the carcinogenicity of this chemical in humans were recently reported. Hospital blood bank facilities and randomly selected volunteers were used for HCB analyses in serum (n = 100) and cerumen (n = 25). Other main organochlorine residues often found in human tissues and blood (pp DDE, beta-HCH,) were also determined. 2. HCB serum levels currently found (Range 0.7-19.7 ng Ml-1; X +/- s.d.: 4.13 +/- 3.61; GM: 3.05) were compared to those found in a similar survey made in 1986 on the same population. The serum HCB levels showed a significant decrease (P < 0.001) when compared to the former results and correlated with age (P < 0.001) suggesting a progressive preponderance of a stable blood-adipose equilibrium with fewer variations due to recent and variable intake of the chemical. 3. Cerumen analyses revealed detectable concentrations of HCB in all samples (Range: 160-4790 ng g-1 in extractable lipid basis) and confirmed the suitability of this matrix to assess the body burden of residues accumulated in adipose and lipid-rich tissues. The set of results shows that, although HCB exposure has been reduced, the overall population under study still accumulates significant amounts of this possible carcinogen.

[Multicenter study comparing the efficacy and tolerance of topical ciprofloxacin (0.3%) versus topical gentamicin (0.3%) in the treatment of simple, non-cholesteatomaous chronic otitis media in the suppurative phase]. / Estudio multicéntrico comparativo de la eficacia y tolerancia de ciprofloxacino tópico (0.3%) versus gentamicina tópica (0.3%) en el tratamiento de la otitis media crónica simple no colesteatomatosa en fase supurativa.

A multicentre double-blind randomized study was carried out to compare topical ciprofloxacin and topical gentamicin in the treatment of simple non-cholesteatomatous purulent chronic otitis media. Three hundred and eight patients were included in the study, 159 treated with ciprofloxacin and 149 treated with gentamicin. The percentage of clinical success (elimination of otorrhoea) was 95% with ciprofloxacin and 94% with gentamicin (ns). Likewise, the percentage of bacteriological erradication was 96% with ciprofloxacin and 93% with gentamicin. Both drugs were well tolerated, without changes in the audiometric values. In these patients, topical ciprofloxacin shows the same efficacy as topical gentamicin without any potential ototoxic effect.