Italian reference rivers under the Water Framework Directive umbrella: do natural factors actually depict the observed nutrient conditions?

Abstract Background Despite the efforts made in the last century to counteract the nutrient enrichment from diffuse and point-sources, the excess of nitrogen and phosphorous is among the main causes of degradation of European rivers. In this context, determining natural background concentrations of nutrients in rivers is crucial for a correct definition of their ecological status. In the most anthropized regions, this is a difficult task. This study provides a nation-wide assessment of the nutrient concentration variability between Italian river reference sites. Results We applied the Affinity Propagation technique to identify groups of river sites classified as reference based on measured nutrients and oxygen water saturation. The role of natural and anthropogenic factors determining differences in nutrients concentration between groups of sites was explored. Nitrate concentrations varied from 0.01 mg N l−1 to more than 5 mg N l−1. Ammonia and total phosphorous varied between 0.001 and 0.12 mg l−1. Observed nutrient levels, although in line with those identified for reference sites in other countries, largely exceed the ranges reported for natural basins. Atmospheric deposition of inorganic N and artificial and/or high-impact agricultural land use are the major factors determining differences in nutrient concentration. Factors like, e.g. catchment size, precipitation amount and altitude do not play a relevant role in explaining nutrient differences between groups of reference sites. Conclusions We especially focused on (i) major causes of failure in the selection of appropriate reference sites in Italy; (ii) the potential of setting higher NO3-N thresholds for the classification of ecological status in specific areas, and (iii) the prospective of a regionalization approach, in which human effects are accepted to a low degree for reference site selection or when setting thresholds for peculiar geographical areas

The ratio of lentic to lotic habitat features strongly affects macroinvertebrate metrics used in southern Europe for ecological status classification

Abstract Biological quality in rivers based on benthic macroinvertebrates is typically assessed by comparison with expected reference conditions, which represent relatively undisturbed situations. Commonly, reference conditions are set in agreement with river typologies to handle major ecological differences and limit biological variability. Although natural hydrological variation can be highly influential, site-specific tuning of reference conditions is rare in Mediterranean countries. River flow and local hydraulics change continuously over time, shaping the occurrence of lentic and lotic habitat features. Thus, biological reference conditions might require site-specific adjustment based on the ratio of lentic to lotic habitats assessed at the time of sampling. This would help reducing systematic bias in ecological assessments, interpreting benthic invertebrate responses to pressures, and diminishing the amount of unexplained biological variability. In this study, the response to the lentic-lotic character of river reaches was assessed for nineteen macroinvertebrate metrics and indices commonly used for the classification of ecological status in South European rivers. The study sites, with a prevalent temporary character, were located in Sardinia, southwestern Italy. Most metrics were significantly related to the lentic-lotic habitat conditions, both in pool and riffle mesohabitats, and their response curves were either parabolic or linearly decreasing at increasing lentic conditions. Taxonomic richness, score-based metrics, ovoviviparous taxa and multi-metric indices related well to the lentic-lotic conditions, while abundance metrics correlated less. The potential impact on ecological status classification was tested for the method formally used in Italy, which had a major role in comparing and inter-calibrating European assessment methods for the Water Framework Directive. After adjusting for bias due to the ratio of lentic to lotic habitat features, quality classification shifted towards better ecological status for ≈ 23% samples. This highlighted the impact of ignoring lentic-lotic information when defining reference conditions for assessing ecological status, varying from difficulties in understanding the biological response to pressures, to largely biased ecological status classification. The observed response of macroinvertebrate metrics to lentic-lotic conditions should be a key consideration for realistic ecological status assessment and could further be a valuable input for evaluating the effects of human-induced hydrological alteration and for assessing environmental flows

Spatial scale effects on taxonomic and biological trait diversity of aquatic macroinvertebrates in Mediterranean streams

We examined the effect of spatial scale on aquatic macroinvertebrate communities in Mediterranean streams from six basins distributed across southern Europe, including Spain, France, Italy, and Greece. We classified the studied streams according to their long-term aquatic regime into the three following types: (i) permanent (P), (ii) intermittent with summer pools (I-P), and (iii) intermittent with summer dry channels (I-D). For each stream type, we analyzed taxonomic and trait diversity, as well as the composition of the macroinvertebrate community, following a spatially nested design at three spatial scales of analysis: microhabitat (substratum patches), mesohabitat (pools vs. riffles), and macrohabitat (streams). In order to assess intrinsic seasonal variability in streams from the Mediterranean region, 20 Surber samples were taken from each stream according to meso- and microhabitat frequency in the wet and the dry season during 2010. Given the need for adaptation to specific hydrological conditions and the fact that microhabitats should encompass the niche requirements of particular taxa, we hypothesized that this spatial scale would have a greater influence on macroinvertebrate taxa composition and biological traits than the other two larger spatial scales in intermittent streams. We observed that patterns in the relative importance of variance components across hierarchical spatial scales changed with time because low flow or droughts altered both mesohabitat preva - lence and microhabitat composition. Our results confirm the importance of the microhabitat scale in I-P streams in the wet season but not in the dry one, when a loss of microhabitat diversity occurred. Stream-to-stream variability was more important in P and I-D streams. Our study also explored the relationships between traits and aquatic regimes. We found that aquatic macroinvertebrates inhabiting permanent streams exhibited traits related to the longer duration of life cycles in these rivers (e.g. large size of adult stages) and adaptations to flowing conditions (e.g. modes of aquatic dispersal), whereas aquatic macroinvertebrates inhabiting intermittent streams with summer pools had traits adapted to depositional conditions and ecological preferences for confined habitats (i.e. disconnected pools without flow). Finally, aquatic macroinvertebrates from intermittent streams with summer dry channels had adaptations conferring ability to survive periods with no water (e.g. modes of aerial dispersal, resistant stages). These results indicate that microhabitat conditions should not be neglected as they can play an important role in certain situations

A biological tool to assess flow connectivity in reference temporary streams from the Mediterranean Basin

Many streams in the Mediterranean Basin have temporary flow regimes. While timing for seasonal drought is predictable, they undergo strong inter-annual variability in flow intensity. This high hydrological variability and associated ecological responses challenge the ecological status assessment of temporary streams, particularly when setting reference conditions. This study examined the effects of flow connectivity in aquatic macroinvertebrates from seven reference temporary streams across the Mediterranean Basin where hydrological variability and flow conditions are well studied. We tested for the effect of flow cessation on two streamflow indices and on community composition, and, by performing random forest and classification tree analyses we identified important biological predictors for classifying the aquatic state either as flowing or disconnected pools. Flow cessation was critical for one of the streamflow indices studied and for community composition. Macroinvertebrate families found to be important for classifying the aquatic state were Hydrophilidae, Simuliidae, Hydropsychidae, Planorbiidae, Heptageniidae and Gerridae. For biological traits, trait categories associated to feeding habits, food, locomotion and substrate relation were the most important and provided more accurate predictions compared to taxonomy. A combination of selected metrics and associated thresholds based on the most important biological predictors (i.e. Bio-AS Tool) were proposed in order to assess the aquatic state in reference temporary streams, especially in the absence of hydrological data. Although further development is needed, the tool can be of particular interest for monitoring, restoration, and conservation purposes, representing an important step towards an adequate management of temporary rivers not only in the Mediterranean Basin but also in other regions vulnerable to the effects of climate change

Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children

Background: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children  25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML. METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission with full or partial hematologic recovery. Secondary end points included event-free survival (freedom from treatment failure [i.e., relapse or lack of remission] or death) and the percentage of patients who had complete remission. RESULTS: Of 371 eligible patients, 247 were randomly assigned to the gilteritinib group and 124 to the salvage chemotherapy group. The median overall survival in the gilteritinib group was significantly longer than that in the chemotherapy group (9.3 months vs. 5.6 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P\u3c0.001). The median event-free survival was 2.8 months in the gilteritinib group and 0.7 months in the chemotherapy group (hazard ratio for treatment failure or death, 0.79; 95% CI, 0.58 to 1.09). The percentage of patients who had complete remission with full or partial hematologic recovery was 34.0% in the gilteritinib group and 15.3% in the chemotherapy group (risk difference, 18.6 percentage points; 95% CI, 9.8 to 27.4); the percentages with complete remission were 21.1% and 10.5%, respectively (risk difference, 10.6 percentage points; 95% CI, 2.8 to 18.4). In an analysis that was adjusted for therapy duration, adverse events of grade 3 or higher and serious adverse events occurred less frequently in the gilteritinib group than in the chemotherapy group; the most common adverse events of grade 3 or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%). CONCLUSIONS: Gilteritinib resulted in significantly longer survival and higher percentages of patients with remission than salvage chemotherapy among patients with relapsed or refractory FLT3-mutated AML. (Funded by Astellas Pharma; ADMIRAL ClinicalTrials.gov number, NCT02421939.)

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection