Plos One
-
Randomized Controlled Trial
A randomized, observer-blinded immunogenicity trial of Cervarix(®) and Gardasil(®) Human Papillomavirus vaccines in 12-15 year old girls.
The current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals. ⋯ These data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines.
-
Randomized Controlled Trial
Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).
The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), a placebo-controlled trial of pravastatin, demonstrated a 19% reduction in coronary outcomes (p=0.006) after a mean of 3.2 years, with no impact on stroke outcomes or all-cause mortality. However, there was a suggestion of increased cancer risk. Our aim is to determine the long-term benefits and safety of pravastatin treatment in older people using post-trial follow-up of the PROSPER participants. ⋯ Pravastatin treatment of elderly high-risk subjects for 3.2 years provided long-term protection against CHD events and CHD mortality. However, this was not associated with any increase in life expectancy, possibly due to competing mortality with deaths from other causes. There was no evidence of long-term increased risk of cancer.
-
Randomized Controlled Trial
Prenatal vitamin d supplementation and child respiratory health: a randomised controlled trial.
Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study. ⋯ Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years.
-
Randomized Controlled Trial
Neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer receiving palliative chemotherapy: a randomized phase II study.
A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC). Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES) of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting. ⋯ NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.
-
Randomized Controlled Trial
Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation.
Nasal potential difference (NPD) is used as a biomarker of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) activity. We evaluated methods to detect changes in chloride and sodium transport by NPD based on a secondary analysis of a Phase II CFTR-modulator study. Thirty-nine subjects with CF who also had the G551D-CFTR mutation were randomized to receive ivacaftor (Kalydeco™; also known as VX-770) in four doses or placebo twice daily for at least 14 days. ⋯ Based on our findings, NPD studies should assess both nostrils rather than a single nostril. We also found that changes in CFTR activity were more readily detected than changes in ENaC activity, and that rigorous standardization was associated with relatively good within-subject reproducibility in placebo-treated subjects (± 2.8 mV). Therefore, we have confirmed an assay of reasonable reproducibility for detecting chloride-transport improvements in response to CFTR modulation.