Simultaneous Determination of Fluoroquinolones and Sulfonamides Originating from Sewage Sludge Compost

A simultaneous method for quantitative determination of traces of fluoroquinolones (FQs) and sulfonamides (SAs) in edible plants fertilized with sewage sludge was developed. The compounds were extracted from the plants by rapid and simple liquid extraction followed by extracts clean-up using solid phase extraction. The eluent additive 1,1,1,3,3,3-hexafluoro-2-propanol was used for liquid chromatographic detection to achieve separation of structurally similar antimicrobials like ciprofloxacin and norfloxacin. Identification and quantification of the compounds were performed using high-performance liquid chromatography with electrospray ionization mass spectrometry in selected reaction monitoring mode. Method was validated and extraction recoveries of FQs and SAs ranged from 66% to 93%. The limit of quantifications was from 5 ng/g in the case of ofloxacin to 40 ng/g for norfloxacin. The method precision ranged from 1.43% to 2.61%. The developed novel method was used to evaluate the plats antimicrobial uptake (potato (Solanum tuberosum L.), carrot (Daucus carota L.), lettuce (Lactuca sativa L.), and wheat (Triticum vulgare L.)) from soil and migration of the analytes inside the plants

Pharmacokinetics of penicillin G in preterm and term neonates.

Group B streptococci are common causative agents of early-onset neonatal sepsis (EOS). Pharmacokinetic (PK) data for penicillin G have been described for extremely preterm neonates but poorly for late-preterm and term neonates. Thus, evidence-based dosing recommendations are lacking. We described PK of penicillin G in neonates with gestational age (GA) ≥32 weeks and postnatal age 90% for MICs ≤2 mg/L with doses of 25,000 IU/kg/q12h. In neonates, regardless of GA, PK parameters of penicillin G are similar. The dose of 25,000 IU/kg/q12h is suggested for treatment of group B streptococcal EOS diagnosed within the first 72 hours of life

Shallow and Deep Groundwater Moderate Methane Dynamics in a High Arctic Glacial Catchment

Glacial groundwater can mobilize deep-seated methane from beneath glaciers and permafrost in the Arctic, leading to atmospheric emissions of this greenhouse gas. We present a temporal, hydro-chemical dataset of methane-rich groundwater collected during two melt seasons from a high Arctic glacial forefield to explore the seasonal dynamics of methane emissions. We use methane and ion concentrations and the isotopic composition of water and methane to investigate the sources of groundwater and the origin of the methane that the groundwater transports to the surface. Our results suggest two sources of groundwater, one shallow and one deep, which mix, and moderate methane dynamics. During summer, deep methane-rich groundwater is diluted by shallow oxygenated groundwater, leading to some microbial methane oxidation prior to its emergence at the surface. Characterization of the microbial compositions in the groundwater shows that microbial activity is an important seasonal methane sink along this flow-path. In the groundwater pool studied, we found that potential methane emissions were reduced by an average of 29% (±14%) throughout the summer due to microbial oxidation. During winter, deep groundwater remains active while many shallow systems shut down due to freezing, reducing subsurface methane oxidation, and potentially permitting larger methane emissions. Our results suggest that ratios of the different groundwater sources will change in the future as aquifer capacities and recharge volumes increase in a warming climate

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - An observational study in 29 countries

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (V T) size was 500 ml, or 7 to 9 ml kg−1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P ˂ 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P ˂ 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high V T and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome.</p

Pre-elimination of malaria on the island of Príncipe

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>is the major species responsible for malaria transmission on the island of Príncipe, in the Republic of São Tomé and Príncipe (STP). Indoor residual spraying (IRS) has been intensively deployed on the island, since 2003. Other measures included intermittent preventive therapy (IPT), since 2004, as well as artemisinin-based therapy (ACT) and long-lasting insecticidal nets (LLINs) from 2005. The work was coordinated by the Ministry of Health of STP through their Centro Nacional de Endemias (CNE) and the impact of such an integrated control programme on the prevalence and epidemiology of malaria in Príncipe was evaluated.</p> <p>Methods</p> <p>The scaling-up of preventive strategies included IRS, LLINs, IPT for pregnant women, as well as early diagnosis and prompt treatment with ACT. Regular implementation of an island-wide IRS programme was carried out yearly in 2003-2005, and later in 2008. Malaria incidence and prevalence were estimated based on passive case detection and active case detection, respectively. Slide positivity rate (SPR) was used as an indicator of any increase of malaria cases during and after the control programme was initiated.</p> <p>Results</p> <p>Regular IRS achieved a coverage of 85-90% for each of the four annual cycles (2003-2005, annually and one spraying in 2008) while usage of LLINs was never superior to 50% from 2006-2009. Coverage of IPT steadily increased from 50% in 2004 to 80% in 2008. Since 2006, over 90% of uncomplicated malaria patients received ACT treatment. Severe malaria cases were hospitalized and treated with quinine. Monthly trends of SPR were constantly over 50% in 2003, but steadily decreased below 10% in 2006. SPR has been below 5% since 2007, but an increase to up to 15% was noted in June 2009 when 16 imported cases were detected. A steep decline by 99% of malaria incidence was observed between 2003 and 2008, with an incidence risk of the population of five per thousand, in 2008. No malaria mortality has been reported since 2005. Species shift from falciparum to non-falciparum malaria was noted after a five-year intensive control programme. Cross-sectional country-wide active surveillances showed malaria prevalences of 1.1%, 0.7%, and 0.9% in June 2006, Oct 2007, and July 2009, respectively, of which over 90% were asymptomatic.</p> <p>Conclusion</p> <p>The effective measures of the combination of four major control methods have produced a rapid decline in malaria morbidity and mortality on the island of Príncipe. The combination of IRS, IPT, and active surveillance with ACT treatment seemed to have played important roles to achieve a present status of low and stable malaria on the island. In low transmission settings, any increase of malaria morbidity indicates potential epidemics and assumes that current control strategies were interrupted. Active surveillance should be reinforced to follow and monitor all asymptomatic carriers and imported cases. Consolidation and a shift to elimination phase demands the sustainability of such integrated programmes.</p

Potential threat of malaria epidemics in a low transmission area, as exemplified by São Tomé and Príncipe

Abstract Background Plasmodium falciparum is the major cause of malaria infection in the island of São Tomé, in the Republic of São Tomé and Príncipe (STP), with an incidence of 40 - 50% before 2004. Since 2004, through the coordination of the Ministry of Health of STP and their Centro Nacional de Endemias (CNE), an integrated malaria control programme has been intensively deployed on the island of São Tomé. Malaria morbidity and mortality decreased by 95% after three years of effective intervention. In the low transmission settings, however, malaria seasonal fluctuation can be a potential problem directly related to epidemics if ongoing control measures are interrupted. Studies on a number of associated factors with malaria epidemics and the measures taken to respond to outbreaks are presented. Methods The integrated malaria control programme included indoor residual spraying (IRS), long-lasting insecticidal nets (LLINs), intermittent preventive therapy for pregnant women, as well as early diagnosis and prompt treatment with artemisinin-based combination therapy (ACT). Regular implementation of an island-wide IRS programme was carried out yearly in 2004-2007, and enhanced throughout the island in 2009. Malaria incidence and prevalence were estimated based on passive case detection and mass screening, respectively. Slide positivity rates were used for monitoring the beginning of a malaria epidemic or a seasonal peak. Results A steep decline of ca. 95% of malaria morbidity and mortality was observed between 2004 and 2008 with use of the combined control methods. Malaria incidence was 2.0%, 1.5%, and 3.0% for 2007, 2008, and 2009, respectively. In April 2008, a cross-sectional country-wide surveillance showed malaria prevalence of 3.5%, of which 95% cases were asymptomatic carriers. Only 50% of asymptomatic carriers were cured with ACT treatment, while 90% of the symptomatic patients were cured by ACT treatment as confirmed with a follow up study. Malaria morbidity increased by three-fold during the first half of 2009 as compared to the same period in 2008. Over this period of six months, severe malaria was also noted in all age groups and malaria mortality increased by two-fold in children less than five years old. After an emergency IRS was deployed, with increased use of LLINs, and an active search of asymptomatic carriers was followed and given complete ACT treatment, malaria incidence decreased to less than 1% in the second half of 2009. Conclusion At the initial stage of the integrated malaria control programme, IRS contributed to the visible effect on the rapid reduction of malaria morbidity and mortality, while this programme highlights an urgent demand for the improvement of other measures, particularly promotion of LLINs usage, with close monitoring of asymptomatic carriers and with ACT treatment in malaria transmission hotspots. In addition, both daily reports and a regular active surveillance to prevent malaria outbreaks should be established permanently, so that a fast response to epidemics can be effectively made when necessary.</p