Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Scrub Typhus Is an Under-recognized Cause of Acute Febrile Illness with Acute Kidney Injury in India

<div><p>Background</p><p>Infection-related acute kidney injury (AKI) is an important preventable cause of morbidity and mortality in the tropical region. The prevalence and outcome of kidney involvement, especially AKI, in scrub typhus is not known. We investigated all patients with undiagnosed fever and multisystem involvement for scrub typhus and present the pattern of renal involvement seen.</p><p>Methods</p><p>From September 2011 to November 2012, blood samples of all the patients with unexplained acute febrile illness and/or varying organ involvement were evaluated for evidence of scrub typhus. A confirmed case of scrub typhus was defined as one with detectable <i>Orientia tsutsugamushi</i> deoxyribonucleic acid (DNA) in patient's blood sample by nested polymerase chain reaction (PCR) targeting the gene encoding 56-kDa antigen and without any alternative etiological diagnosis. Renal involvement was defined by demonstration of abnormal urinalysis and/or reduced glomerular filtration rate. AKI was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) definition.</p><p>Results</p><p>Out of 201 patients tested during this period, 49 were positive by nested PCR for scrub typhus. Mean age of study population was 34.1±14.4 (range 11–65) years. Majority were males and a seasonal trend was evident with most cases following the rainy season. Overall, renal abnormalities were seen in 82% patients, 53% of patients had AKI (stage 1, 2 and 3 in 10%, 8% and 35%, respectively). The urinalysis was abnormal in 61%, with dipstick positive albuminuria (55%) and microscopic hematuria (16%) being most common. Acute respiratory distress syndrome (ARDS) and shock were seen in 57% and 16% of patients, respectively. Hyperbilirubinemia was associated with AKI (p = 0.013). A total of 8 patients (including three with dialysis dependent AKI) expired whereas rest all made uneventful recovery. Jaundice, oliguria, ARDS and AKI were associated with mortality. However, after multivariate analysis, only oliguric AKI remained a significant predictor of mortality (p = 0.002).</p><p>Conclusions</p><p>Scrub typhus was diagnosed in 24% of patients presenting with unexplained febrile illness according to a strict case definition not previously used in this region. Renal abnormalities were seen in almost 82% of all patients with evidence of AKI in 53%. Our finding is contrary to current perception that scrub typhus rarely causes renal dysfunction. We suggest that all patients with unexplained febrile illness be investigated for scrub typhus and AKI looked for in scrub typhus patients.</p></div

Nitroethylene: a stable, clean, and reactive agent for organic synthesis

Contrary to current belief, nitroethylene is a stable reagent and holds promise as a useful and reactive synthon.Nitroethylene can be prepared in 20-25-g lots, and standard, refrigerated solutions in common solvents providea good and ready source of the reagent. The reagent purity can be easily monitored by titration againsttetraphenylcyclopentadienone (tetracyclone) coupled with the isolation of the colorless crystalline adduct. Withreactive substrates, nitroethylene reacts with greatest ease at low temperatures, leading to functionalized systemshaving potential for further elaboration. With systems that require heating, the limited stability of nitroethyleneitself complicates the course of the reaction. Cyclopentadiene, 5-[ (benzyloxy)methyl]cyclopentadiene,5 -(methoxymethyl)cyclopentadiene, 5-(1,3-dithianyl)cyclopentadiene, 5-(trimethylsilyl)cyclopentadiene, andspiroheptadiene readily gave (4 + 2) adducts with nitroethylene, each possessing attraction as a syntheticintermediate. Adducts from furan and acetoxyfulvene undergo rearrangement via u cleavage. The (4 + 2) adductfrom 9-diazofluorene spontaneously extrudes nitrogen, leading to spironitrocyclopropane. Indole readily undergoesMichael addition to give 80% 3-(nitroethy1)indole and 15% of novel bis adduct. The 2,6 Michael adduct ariseswith 1-morpholinocyclohexene, and @-pinene undergoes an ene reaction with nitroethylene. Novel 2-nitroethylphosphonates, useful in Wittig-Hornerreactions, arise from nitroethylene and phosphites in tert-butyl alcohol

The ethidium bromide-stained agarose gel shows the 483 bp polymerase chain reaction products.

<p>L: 500 bp ladder, 1–4: patients' samples; 5: positive control; 6: negative control.</p

Renal involvement in scrub typhus.

<p>Used ≥4 fold rise in antibody titre in paired serum samples if diagnosed by IFA.</p><p>AKIN: Acute Kidney Injury Network, ELISA: Enzyme Linked Immunosorbent Assay, IgM: Immunoglobulin M.</p

Renal abnormalities in the confirmed scrub typhus study population (no. of patients: 49).

<p>^# excludes two patients with gross hematuria;</p><p>defined according to KDIGO guidelines for AKI.</p><p>AKI: acute kidney injury, KDIGO: Kidney Disease: Improving Global Outcomes, RBC: red blood cell.</p

Diagnoses in scrub typhus PCR negative population.

<p>Drug Reaction with Eosinophila and Systemic Symptoms (DRESS);</p><p>^# Still's disease, erythema nodosum, polymyositis, dapsone syndrome, thrombotic microangiopathy.</p><p>ELISA: enzyme linked immunosorbent assay, IgM: immunoglobulin M, PCR: polymerase chain reaction.</p