Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Acknowledgments: We thank all the women who participated in this trial; the participating general practitioners, gynecologists, and hospitals; the research nurses; and the staff of the Dutch Consortium for Studies in Women’s Health and Reproduction.Peer reviewedPublisher PD

Safety and efficacy of Monteban® G100 (narasin) for chickens for fattening

The feed additive Monteban\uae G100, containing the active substance narasin, an ionophore anticoccidial, is intended to control coccidiosis in chickens for fattening at a dose of 60\u201370 mg/kg complete feed. Narasin is produced by fermentation. Limited data on the taxonomic identification of the production strain did not allow the proper identification of strain NRRL 8092 as Streptomyces aureofaciens. The FEEDAP Panel cannot conclude on the absence of genetic determinants for antimicrobial resistance in Streptomyces spp. under assessment. Based on the available data set, the FEEDAP Panel cannot conclude on the safety of Monteban\uae G100 for chickens for fattening. The simultaneous use of Monteban\uae G100 and certain antibiotic drugs (e.g. tiamulin) is contraindicated. Narasin is not genotoxic. No indication of carcinogenicity or developmental toxicity was found at the doses tested in the mouse, rat and rabbit. The lowest no observed effect level (NOEL) identified in the oral toxicity studies was 0.5 mg/kg body weight (bw) per day for the neuropathy seen in a one-year dog study. The acceptable daily intake (ADI) derived from this NOEL is 0.005 mg narasin/kg bw applying a uncertainty factor of 100. Monteban\uae G100 is safe for the consumer. Maximum residue limits (MRLs) of 50 lg narasin/kg for all wet tissues ensure consumer safety. Monteban\uae G100 is irritatant to the eyes but not to the skin. It has the potential to induce skin sensitisation. Inhalation exposure would pose a risk to persons handling the additive. Narasin, when used as a feed additive for chickens for fattening at 70 mg/kg feed, is not expected to pose a risk to the environment. The risk for sediment compartment cannot be assessed. The FEEDAP Panel cannot conclude on the efficacy of Monteban\uae at the minimum applied dose of 60 mg narasin/kg complete feed for chickens for fattening

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Pollution-Induced Community Tolerance of Soil Microbial Commuinities Caused by the Antibiotic Sulfachloropyridazine.

Abstract not availableJRC.I-Institute for Health and Consumer Protection (Ispra

ON THE LIMITS OF TOXICANT-INDUCED TOLERANCE TESTING: COTOLERANCE AND RESPONSE VARIATION OF ANTIBIOTIC EFFECTS

Pollution-induced community tolerance (PICT) as an ecotoxicological test system has been claimed to detect pollutant effects highly specifically and sensitively. However, the specificity might be limited by the occurrence of cotolerance. Another limitation of the application of any ecotoxicological test system lies in variation of the measured responses. We tested the variation and the occurrence of cotolerance experimentally, using antibiotics as toxicants, soil microcosms as microbial communities, and tolerance determination in Biolog plates as PICT detection test. Bacteria have been discussed as being prone to multiple tolerances due to the possible accumulation of multiple resistance genes on mobile genetic elements. However, in our experiments, cotolerance occurred only between antibiotics of the same group (oxytetracycline and tetracycline), as expected from their identical mode of action. Cotolerance between oxytetracycline and tylosin in soil microcosms exposed to oxytetracycline was low, as was cotolerance to oxytetracycline in tylosin-exposed microcosms. We conclude that tolerance development to antibiotics in soils reflects the actual selection pressure rather than a general pattern of multiple resistances. Concerning variation, the PICT effect of tetracycline was well reproducible in two consecutive years. The response variation linked to PICT experiments in controlled microcosms was comparable to that of ecotoxicological test systems of equivalent complexity. In conclusion, our results support an application of the PICT methodology as an effective means to study the soil ecotoxicology of antibiotics

On the limits of toxicant-induced tolerance testing: cotolerance and response variation of antibiotic effects.

Pollution-induced community tolerance (PICT) as an ecotoxicological test system has been claimed to detect pollutant effects highly specifically and sensitively. However, the specificity might be limited by the occurrence of cotolerance. Another limitation of the application of any ecotoxicological test system lies in variation of the measured responses. We tested the variation and the occurrence of cotolerance experimentally, using antibiotics as toxicants, soil microcosms as microbial communities, and tolerance determination in Biolog plates as PICT detection test. Bacteria have been discussed as being prone to multiple tolerances due to the possible accumulation of multiple resistance genes on mobile genetic elements. However, in our experiments, cotolerance occurred only between antibiotics of the same group (oxytetracycline and tetracycline), as expected from their identical mode of action. Cotolerance between oxytetracycline and tylosin in soil microcosms exposed to oxytetracycline was low, as was cotolerance to oxytetracycline in tylosin-exposed microcosms. We conclude that tolerance development to antibiotics in soils reflects the actual selection pressure rather than a general pattern of multiple resistances. Concerning variation, the PICT effect of tetracycline was well reproducible in two consecutive years. The response variation linked to PICT experiments in controlled microcosms was comparable to that of ecotoxicological test systems of equivalent complexity. In conclusion, our results support an application of the PICT methodology as an effective means to study the soil ecotoxicology of antibiotics

Análisis de los conflictos entre comunidades locales y autoridades de conservación en Colombia. Causas y recomendaciones

Conflicts between indigenous and local communities, on the one hand, and national protected area administrations on the other are pervasive. A better understanding of these park-people conflicts would assist in suitable policy changes to constructively address them while concurrently pursuing conservation and livelihood goals. We interviewed 601 people living inside or along the borders of fifteen Colombian NPAs to identify five main categories of park-people conflicts. Based on interviews with 128 community leaders and 76 institutional-level respondents -mainly park officers- we discuss the five principal factors underlying the identified conflicts and present a conflict framework relating the dominant sources to the most prominent conflict manifestations. Finally, we detail five strategies toward conflict prevention. While simultaneous interventions at multiple levels would be ideal or preferred, our analysis suggests that the incidence of park-people conflicts in Colombia can be substantially lowered through (i) making the environmental legislative body more socially inclusive; and (ii) adequately empowering NPA administrations. We expect our findings to be valuable for managing conflict contexts in protected areas in other tropical countries. Further research is necessary to determine the most effective interventions for both conflict resolution and meeting conservation goals.Los conflictos entre las comunidades indígenas y locales, por un lado, y las administraciones de áreas protegidas, por el otro, son numerosos. Entender mejor estos conflictos es esencial para desarrollar políticas adecuadas que aborden estos conflictos de manera constructiva y al mismo tiempo contribuyan a lograr objetivos de conservación. Entrevistamos a 601 personas que vivían dentro o a lo largo de las fronteras de quince parques nacionales Colombianos para identificar cinco categorías de conflictos entre los parques y la gente. Con base en entrevistas con 128 líderes comunitarios y 76 responsables a nivel institucional – agentes de los parques, principalmente -, se discuten en mayor profundidad los cinco factores principales subyacentes en los conflictos identificados y presentamos un marco de conflicto que relaciona las fuentes dominantes con las manifestaciones de tales conflictos. Finalmente, detallamos cinco estrategias para la prevención de conflictos. Pese a que una intervención simultánea en múltiples niveles sería lo más efectivo, el análisis muestra que una fuerte inversión en sólo dos áreas de interés podría reducir considerablemente la incidencia de los principales conflictos identificados: (i) ajustar la legislación ambiental para hacerla socialmente más incluyente; y (ii) empoderar adecuadamente a los administradores de los parques