Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience

Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.     

Clinical pharmacology of GW280430A in humans

BACKGROUND: An ultrashort-acting nondepolarizing neuromuscular blocking agent that could be an alternative to succinylcholine has been the focus of a concerted effort in the field of muscle relaxants. GW280430A showed a promising pharmacodynamic profile in preclinical work and a wide margin of safety and so was selected for study in humans. METHODS: Thirty-one volunteers participated in this study, which determined the dose producing 95% block (ED95) and the safety and pharmacodynamics of increasing ED95 multiples. Anesthesia was induced and maintained with propofol, midazolam, and fentanyl. Neuromuscular transmission was measured at the adductor pollicis using ulnar nerve stimulation, and responses were recorded continuously by standard mechanomyographic monitoring. RESULTS: The ED95 for GW280430A is 0.19 mg/kg. The time to onset of 90% block ranged from 1.3 to 2.1 min, depending on the dose. Clinical durations ranged from 4.7 to 10.1 min and increased with increasing dose. Five to 95% and 25-75% recovery rates were approximately 7 and 3 min, respectively, and were independent of the dose administered. Transient cardiovascular side effects were observed at doses beginning at 3 x ED95 and above and were suggestive of histamine release. Most volunteers receiving 4 x ED95 exhibited plasma histamine concentrations indicative of significant histamine release. CONCLUSIONS: GW280430A has a rapid onset and ultrashort duration of action. The recovery rate is rapid, predictable, and independent of dose. Doses at least up to 2.5 x ED95 seem to be free of side effects and seem to be able to provide relaxation within 60-90 s.     

Dexmedetomidine and neurocognitive testing in awake craniotomy

Patients are selected for awake craniotomy when the planned procedure involves eloquent areas of the brain, necessitating an awake, cooperative patient capable of undergoing neurocognitive testing. Different anesthetic combinations, including neurolept, propofol with or without opioid infusions, and asleep-awake-asleep techniques, have been reported for awake craniotomy. In all these techniques, respiratory depression has been reported as a complication. In this case series dexmedetomidine, the highly selective alpha-2 adrenoreceptor agonist, was selected for its lack of respiratory depression as well as its sedative and analgesic properties. The charts of 10 consecutive patients who underwent awake craniotomy with dexmedetomidine infusion were reviewed. Five of the patients underwent "asleep-awake" technique with a laryngeal mask airway and volatile agent. Five patients received moderate to conscious sedation. All patients received a dexmedetomidine load of 0.5 to 1.0 microg/kg over 20 minutes followed by an infusion at rates of 0.01 to 1.0 microg/kg per hour. Four patients had extensive sensory and motor testing, and six underwent neurocognitive testing, including naming, reading, counting, and verbal fluency. There were no permanent neurologic deficits, except one patient who had an exacerbation of preoperative language difficulties. Dexmedetomidine appears to be a useful sedative for awake craniotomy when sophisticated neurologic testing is required.     

Clinical Pharmacology of GW280430A in Humans

Background: An ultrashort-acting nondepolarizing neuromuscular blocking agent that could be an alternative to succinylcholine has been the focus of a concerted effort in the field of muscle relaxants. GW280430A showed a promising pharmacodynamic profile in preclinical work and a wide margin of safety and so was selected for study in humans.

Methods: Thirty-one volunteers participated in this study, which determined the dose producing 95% block (ED95) and the safety and pharmacodynamics of increasing ED95 multiples. Anesthesia was induced and maintained with propofol, midazolam, and fentanyl. Neuromuscular transmission was measured at the adductor pollicis using ulnar nerve stimulation, and responses were recorded continuously by standard mechanomyographic monitoring.

Results: The ED95 for GW280430A is 0.19 mg/kg. The time to onset of 90% block ranged from 1.3 to 2.1 min, depending on the dose. Clinical durations ranged from 4.7 to 10.1 min and increased with increasing dose. Five to 95% and 25-75% recovery rates were approximately 7 and 3 min, respectively, and were independent of the dose administered. Transient cardiovascular side effects were observed at doses beginning at 3 x ED95 and above and were suggestive of histamine release. Most volunteers receiving 4 x ED95 exhibited plasma histamine concentrations indicative of significant histamine release.     

Isolation and characterization of equine influenza virus (H3N8) from an equine influenza outbreak in Malaysia in 2015

Equine influenza is a major cause of respiratory infections in horses and can spread rapidly despite the availability of commercial vaccines. In this study, we carried out molecular characterization of Equine Influenza Virus (EIV) isolated from the Malaysian outbreak in 2015 by sequencing of the HA and NA gene segments using Sanger sequencing. The nucleotide and amino acid sequences of HA and NA were compared with representative Florida clade 1 and clade 2 strains using phylogenetic analysis. The Florida clade 1 viruses identified in this outbreak revealed numerous amino acid substitutions in the HA protein as compared to the current OIE vaccine strain recommendations and representative strains of circulating Florida sub‐lineage clade 1 and clade 2. Differences in HA included amino acids located within antigenic sites which could lead to reduced immune recognition of the outbreak strain and alter the effectiveness of vaccination against the outbreak strain. Detailed surveillance and genetic information sharing could allow genetic drift of equine influenza viruses to be monitored more effectively on a global basis and aid in refinement of vaccine strain selection for EIV.     

Loss of control over eating in overweight youngsters: The role of anxiety,depression and emotional eating

The current study investigated loss of control (LC) over eating and the role of anxiety, depression and emotional eating in a sample of both treatment seeking (N = 115) and non‐treatment seeking (N = 73) overweight youngsters (aged 8–18) using a semi‐structured clinical interview and self‐report questionnaires. It was found that treatment seekers reported twice as much LC (40%) compared to non‐treatment seekers (21%). Cross‐sectional prediction models indicated that increased anxiety was associated with emotional eating and LC. Emotional eating tended to mediate the relationship between anxiety and LC. Increased depression was associated with emotional eating but not with LC. Especially overweight treatment seekers turn out to be at risk for LC. Because LC may develop as a result of inadequate coping with negative emotions like anxiety, obesity treatment should focus on teaching more effective coping strategies. Longitudinal research is recommended to further elaborate affect regulation and LC. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.