29 research outputs found
Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey
Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux
Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19).
BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines
RECENT DEVELOPMENTS ON ALICE (ACCELERATORS AND LASERS IN COMBINED EXPERIMENTS) AT DARESBURY LABORATORY
Abstract Progress made in ALICE (Accelerators and Lasers In Combined Experiments) commissioning and a summary of the latest experimental results are presented in this paper. After an extensive work on beam loading effects in SC RF booster and linac cavities' conditioning, ALICE can now operate in full energy recovery mode at a bunch charge of 40pC, a beam energy of 27.5MeV and train lengths of up to 100µs. This improved operation of the machine has resulted in generation of coherentlyenhanced broadband terahertz radiation with an energy of several tens of microjoules per pulse and in successful demonstration of the Compton Back-Scattering x-ray source experiment. Experiments on the exposure of living cells to terahertz radiation have been started. These and other developments on ALICE are reported. MACHINE STATUS ALICE, an energy-recovery superconducting linac GaAs photocathode lifetime is now sufficiently long for routine ALICE operation at 40pC. Normally cathode recaesiation is performed once a month, when the quantum efficiency decreases from initial ~3% to below ~0.5%. Over the past year, a number of changes in gradient settings of SC cavities (booster and main linac) were made with the aim of optimising the RF set up and to accommodate limitations presented by the RF system. Each of these variations required significant changes in the overall machine set up. It can now be routinely operated at 27.5MeV with the total beam losses not exceeding 5 to 7%. The energy spectrum of the beam exiting the first cavity of the booster (BC1) with the second cavity (BC2) switched off (resulting in a beam energy of 3.9MeV, compared to the nominal injector energy of 6.5MeV) is shown i
Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial
Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council
Epidemiology and treatment outcome of childhood tuberculosis in England and Wales: 1999–2006
Objective: To describe the recent trends in demographic, clinical and microbiological characteristics and outcome of treatment in paediatric cases of tuberculosis. Design: National surveillance study. Setting: England and Wales. Patients: All children under the age of 16 years reported with tuberculosis to the national enhanced surveillance system between 1999 and 2006 were included. Main outcome measures: Proportions, and rates of disease, by demographic characteristics, site of disease, diagnostic delay, culture confirmation, species, drug susceptibility and treatment outcome. Results: 3563 cases of tuberculosis in children were reported between 1999 and 2006. The incidence rate remained stable at around 4.3 per 100 000 (95% CI 4.1 to 4.4). Patients born outside the UK had a tuberculosis rate higher than children born in the UK (37 per 100 000 vs 2.5 per 100 000) and this rate increased over the period. Rates in the black African ethnic group were highest at 88 per 100 000. 60% of children had pulmonary disease, the commonest presentation, but only 948 (27%) had culture confirmed tuberculosis. The median time to diagnosis from onset of symptoms was 37 days (interquartile range 12–89). The proportions of cases with rifampicin, isoniazid and multi-drug resistant isolates were 2.4%, 9.3% and 2.3%, respectively. 88% of children completed treatment and less than 1% died. Conclusions: Overall rates of tuberculosis in children have remained stable, with the majority completing treatment. Rates are, however, highest in children not born in the UK, particularly among certain ethnic minority groups. Levels of drug resistance are also high
Iron-57 and Antimony-121 Mössbauer-Effect Study of Several Spinel Antimonates
The iron - 57 and antimony - 121 Mössbauer - effect spectra of six iron - containing antimonate spinels, of general formula MII 12FeII 3SbV 3O24, where MII is divalent zinc, magnesium, cobalt, and nickel, and the spinel Ni10Fe6Sb2O24 have been measured and the 4.2 K iron - 57 results used to determine the cation distribution between the tetrahedral A and the octahedral B sites. If MII is diamagnetic zinc(II), all the iron(III) is located on the octahedral B site and the ordering temperature is ca. 1.35 K. In the orthorhombic spinel Mg12Fe3Sb3O24, two - thirds of the iron is on the tetrahedral A site and the ordering temperature is ca. 5 K. When MII is nickel(II) and either cobalt(II) or magnesium(II), there is a distinct preference for the nickel(II) to occupy the octahedral B site and, in so doing, to displace some additional iron(III) from these sites onto the tetrahedral A sites. The presence of magnetic cobalt(II) and nickel(II) cations increases the ordering temperature to ca. 200 K in these compounds. In each case the room - temperature spectra show lines corresponding to both tetrahedral and octahedral iron(III) quadrupole - split doublets with typical hyperfine parameters. Below the ordering temperature, each compound shows at least two iron - 57 Mössbauer - effect magnetic sextets with hyperfine fields at 4.2 K of ca. 450 kOe for the tetrahedral site and ca. 530 kOe for the octahedral site. In several instances, a small distribution in the hyperfine field is observed and attributed to the distribution of the cations on the near - neighbor sites. In each compound a few area percent of a paramagnetic impurity is observed in the magnetic spectra, and the nature of this impurity is discussed. The room - temperature antimony - 121 Mössbauer spectra of these materials show an isomer shift typical of antimony(V) and no hyperfine field at the antimony nucleus. Similar results are obtained for Zn12Fe3Sb3O24 and Mg12Fe3Sb3O24 at 4.2 K. However, the compounds containing magnetic MII dications show supertransferred hyperfine fields at the antimony, the magnitudes of which may be related to the nature and distribution of the dications
Homocysteine, folate, methylation, and monoamine metabolism in depression
OBJECTIVES—Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression.
METHODS—In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes.
RESULTS—Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls.
CONCLUSIONS—Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.