Bis(2-benzamido­benzimidazolato-κ2 N 1,O)(N,N-dimethyl­formamide-κO)copper(II)

In the title compound, [Cu(C14H10N3O)2(C3H7NO)], the CuII atom is five-coordinated by two N,O-bidentate 2-benzamido­benzimidazolate anions and one O-coordinated dimethyl­formamide (DMF) mol­ecule, resulting in a distorted square-based pyramidal CuN2O3 geometry for the metal atom, with the DMF O atom at the apical site. In the crystal structure, inter­molecular N—H⋯N hydrogen bonds result in chains of mol­ecules propagating along [100]

1,2-Bis(N′-benzoyl­thio­ureido)benzene

The title compound, C22H18N4O2S2, was characterized by 1H and 13C NMR, solid-state IR spectroscopy and X-ray crystallographic techniques. The crystal structure determination reveals that the twisting modes of the two side arms are different [C—N—C—O and C—N—C—N torsion angles = −1.2 (3) and 1.1 (3)°, respectively, in one arm and 24.1 (3) and −5.1 (3)°, respectively, in the other]. The crystal structure involves N—H⋯O and N—H⋯S hydrogen bonds

Bis(2-{[2-(2-hy­droxy­benzyl­amino)­eth­yl]amino­meth­yl}phenolato-κ3 N,N′,O 1)cobalt(III) nitrate monohydrate

In the title compound, [Co(C16H19N2O2)2]NO3·H2O, the CoIII ion is located on an inversion center and is six-coordinated by two phenolate O atoms and four amino N atoms from two diamine ligands, forming an octa­hedral geometry. The water mol­ecule and the nitrate anion are located close to an inversion center, and are thus equally disordered by symmetry. The crystal packing is stabilized by inter­molecular O—H⋯O hydrogen bonds involving the uncoordinated water mol­ecule and the free phenol hydroxyl group with the nitrate anion. N—H⋯O hydrogen bonds involving the amino groups and the nitrate anions connect the complex mol­ecules along the c axis

Bis(N,N′-dimethyl­ethylenediammonium) tris­(oxalato-κ2 O 1,O 2)cobaltate(II) dihydrate: an ion-pair complex

The CoII ion in the title complex, (C4H14N2)2[Co(C2O4)3]·2H2O, is coordinated by three oxalate ions, resulting in a distorted octa­hedral geometry. Two uncoordinated water mol­ecules are present in asymmetric unit. Inter­molecular N—H⋯O and O—H⋯O hydrogen bonds between the different entities stabilize the crystal structure

Bis{2-amino-2-oxo-N-[(1E)-1-(pyridin-2-yl-κN)ethyl­idene]acetohydrazidato-κ2 N′,O 1}nickel(II)

In the title compound, [Ni(C9H9N4O2)2], the NiII ion is situated on a twofold rotation axis and is coordinated by two O and four N atoms from two tridentate {2-amino-2-oxo-N-[(1E)-1-(pyridin-2-yl-κN)ethyl­idene]acetohydrazidate ligands in a distorted octa­hedral geometry. In the crystal, N—H⋯O and N—H⋯N hydrogen bonds link the mol­ecules into columns in [001]. The porous crystal packing is further stabilized via π–π inter­actions between the pyridine rings of neighbouring mol­ecules [centroid–centroid distance = 3.746 (3) Å] with voids of 270 Å3

Bis(benzohydrazide-κ2 O,N′)bis­(nitrato-κO)copper(II)

In the title compound, [Cu(NO3)2(C7H8N2O)2], the CuII atom is located on a centre of inversion, and is coordinated by two bidentate benzohydrazide ligands and two monodentate nitrate anions in an axially distorted octa­hedral geometry within an N2O4 donor set. The crystal structure is stabilized by N—H⋯O and weak N—H⋯N hydrogen bonds

The Use of Ebola Convalescent Plasma to Treat Ebola Virus Disease in Resource-Constrained Settings: A Perspective From the Field.

The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola virus disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone, and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, nonrandomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea, enrolled 102 patients by 7 July 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. Although no efficacy data are available yet, current field experience supports the safety, acceptability, and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from nontrial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation

Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014-2015 outbreak.

The Ebola virus disease outbreak in 2014-2015 led to a huge caseload with a high case fatality rate. No specific treatments were available beyond supportive care for conditions such as dehydration and shock. Evaluation of treatment with convalescent plasma from Ebola survivors was identified as a priority. We evaluated this intervention in an emergency setting, where randomization was unacceptable. The original trial design was an open-label study comparing patients receiving convalescent plasma and supportive care to patients receiving supportive care alone. The comparison group comprised patients recruited at the start of the trial before convalescent plasma became available, as well as patients presenting during the trial for whom there was insufficient blood group-compatible plasma or no staffing capacity to provide additional transfusions. However, during the trial, convalescent plasma was available to treat all new patients. The design was changed to use a comparator group comprising patients previously treated at the same Ebola treatment center prior to the start of the trial. In the analysis, it was planned to adjust for any differences in prognostic variables between intervention and comparison groups, specifically baseline polymerase chain reaction cycle threshold and age. In addition, adjustment was planned for other potential confounders, identified in the analysis, such as patient presenting symptoms and time to treatment seeking. Because plasma treatment started up to 3 days after diagnosis and we could not define a similar time-point for the comparator group, patients who died before the third day after confirmation of diagnosis were excluded from both intervention and comparison groups in a per-protocol analysis. Some patients received additional experimental treatments soon after plasma treatment, and these were excluded. We also analyzed mortality including all patients from the time of confirmed diagnosis, irrespective of whether those in the trial series actually received plasma, as an intention-to-treat analysis. Per-protocol and intention-to-treat approaches gave similar conclusions. An important caveat in the interpretation of the findings is that it is unlikely that all potential sources of confounding, such as any variation in supportive care over time, were eliminated. Protocols and electronic data capture systems have now been extensively field-tested for emergency evaluation of treatment with convalescent plasma. Ongoing studies seek to quantify the level of neutralizing antibodies in different plasma donations to determine whether this influences the response and survival of treated patients

Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.

BACKGROUND: The case fatality ratio (CFR) of Ebola virus disease (EVD) can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs. METHODS AND FINDINGS: We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%-27%) for low viremia (V < 104.4 copies/ml) to 53% (95% CI 44%-61%) for intermediate viremia (104.4 ≤ V < 105.2 copies/ml) and 81% (95% CI 75%-87%) for high viremia (V ≥ 105.2 copies/ml). Compared to adults (15-44 y old [y.o.]), the CFR was larger in young children (0-4 y.o.) (odds ratio [OR]: 2.44; 95% CI 1.02-5.86) and older adults (≥ 45 y.o.) (OR: 2.84; 95% CI 1.81-4.46) but lower in children (5-14 y.o.) (OR: 0.46; 95% CI 0.24-0.86). An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care. CONCLUSIONS: Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the ability of surveillance systems to detect EVD patients from the different severity strata

Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, \u3e93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%