Objective The objective of the study was to determine the effect of hepatitis C virus (HCV) on selected maternal and infant birth outcomes. Study Design This population-based cohort study using ...Washington state birth records from 2003 to 2005 compared a cohort of pregnant women identified as HCV positive from birth certificate data (n = 506) to randomly selected HCV-negative mothers (n = 2022) and drug-using HCV-negative mothers (n = 1439). Results Infants of HCV-positive mothers were more likely to be low birthweight (odds ratio OR, 2.17; 95% confidence interval CI 1.24, 3.80), to be small for gestational age (OR, 1.46; 95% CI, 1.00, 2.13), to need assisted ventilation (OR, 2.37; 95% CI, 1.46, 3.85), and to require neonatal intensive car unit (NICU) admission (OR, 2.91; 95% CI, 1.86, 4.55). HCV-positive mothers with excess weight gain also had a greater risk of gestational diabetes (OR, 2.51; 95% CI, 1.04, 6.03). Compared with the drug-using cohort, NICU admission and the need for assisted ventilation remained associated with HCV. Conclusion HCV-positive pregnant women appear to be at risk for adverse neonatal and maternal outcomes.
Summary Background Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment ...of C difficile infection. Methods We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov , number NCT02092935. Findings Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation. Interpretation Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted. Funding Wellcome Trust and Summit Therapeutics.
Objective: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Methods: We analyzed cross-sectional data of the multi-site, international ...hospital-based MRI-GENetics Interface Exploration (MRI-GENIE) study (July 1, 2014- March 16, 2019) with clinical brain magnetic resonance imaging (MRI) obtained on admission for index stroke and functional outcome assessment. Post-stroke outcome was determined using the modified Rankin Scale (mRS) score (0-6; 0: asymptomatic; 6 death) recorded between 60-190 days after stroke. Demographics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke) were recorded during index admission. Results: Utilizing the data from 912 acute ischemic stroke (AIS) patients (65+/-15 years of age, 58% male, 57% history of smoking, and 65% hypertensive) in a generalized linear model, brain volume (per 155.1cm^3 ) was associated with age (beta -0.3 (per 14.4 years)), male sex (beta 1.0) and prior stroke (beta -0.2). In the multivariable outcome model, brain volume was an independent predictor of mRS (beta -0.233), with reduced odds of worse long-term functional outcomes (OR: 0.8, 95% CI 0.7-0.9) in those with larger brain volumes. Conclusions: Larger brain volume quantified on clinical MRI of AIS patients at time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of mechanisms of post-stroke recovery.
The human LDH-A and LDH-B cDNAs, containing the coding regions for the L-lactate dehydrogenase A4 (M) and B4 (H) polypeptides respectively have been cloned into Escherichia coli to place the cDNAs ...under the control of hybrid E. coli/Bacillus stearothermophilus transcriptional and translational signals. Human A4- and B4-isoenzymes are produced in E. coli cells harbouring the expression plasmids pHLDHA22 and pHLDHB10 at levels of 6.5 and 1.5% of the soluble protein of the cell, respectively. The tac promoter of these vectors was not induced by isopropyl beta-D-thiogalactopyranoside. The A4 and B4 human isoenzymes synthesized in E. coli were purified to homogeneity and show the same properties as isoenzymes isolated from human tissue. The amino acid sequences of 12 N-terminal residues of the human isoenzymes synthesized in E. coli were determined to be identical to those deduced from the DNA sequence of the cloned cDNAs except that the N-terminal methionine was absent from both. However, in contrast to LDH made in human cells, acetylation of the N-terminal alanine does not take place in E. coli cells.
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