Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence.

In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability

Functional, spectroscopic and structural properties of haemoglobin from chamois (Rupicapra rupicapra) and steinbock (Capra hircus ibex)

The functional and spectroscopic properties of chamois (Rupicapra rupicapra) and steinbock (Capra hircus ibex) haemoglobin (Hb) have been studied with special reference to the action of allosteric effectors and temperature. Moreover, the amino acid sequences of the N-terminal segments of the alpha- and beta-chains have been determined. The present results indicate that chamois and steinbock Hbs display a low affinity for O2, which appears to be modulated in vivo by Cl- ions rather than 2,3-bisphosphoglycerate. The Bohr effect for O2 binding to chamois and steinbock Hb is higher than for reindeer and bovine Hbs, being similar to that of human Hb. Moreover, the temperature-dependence of oxygenation appears intermediate between that of human and reindeer Hbs. E.p.r. and absorption spectroscopic properties of the ferrous nitrosylated derivative of chamois and steinbock Hbs suggest that both haemoproteins are in a low-affinity conformation even in the absence of InsP6. The reduced effect of polyphosphates on the functional and spectroscopic properties of chamois and steinbock Hb agree with amino acid differences in the N-terminal segment of the beta-chains (i.e. the deletion of Val(NA1) and the replacement of His(NA2), present in human Hb, and Gln(NA2), present in horse Hb, by Met). The molecular mechanism modulating the basic reaction of O2 with chamois and steinbock Hb may be linked to specific physiological needs related to the high-altitude habitats of these two animals

Considerations for early acute myocardial infarction rule-out for emergency department chest pain patients: the case of copeptin.

The evaluation of patients admitted at the emergency department (ED) for chest pain is challenging and involves many different clinical specialists including emergency physicians, laboratory professionals and cardiologists. The preferable approach to deal with this issue is to develop joint protocols that will assist the clinical decision-making to quickly and accurately rule-out patients with non life-threatening conditions that can be considered for early and safe discharge or further outpatient follow-up, rule-in patients with acute coronary syndrome and raise the degree of alert of the emergency physicians on non-cardiac life-threatening emergencies. The introduction of novel biomarkers alongside the well-established troponins might support this process and also provide prognostic information about acute short-term or chronic long-term risk and severity. Among the various biomarkers, copeptin measurement holds appealing perspectives. The utility of combining troponin with copeptin might be cost-effective due to the high negative predictive value of the latter biomarker in the rule-out of an acute coronary syndrome. Moreover, in the presence of a remarkably increased concentration (e.g., more than 10 times the upper limit of the reference range), to reveal the presence of acute life-threatening conditions that may not necessarily be identified with the use of troponin alone. The aim of this article is to review current evidence about the clinical significance of copeptin testing in the ED as well as its appropriate placing within diagnostic protocols. \ua9 2012 by Walter de Gruyter Berlin Boston

Considerations for early acute myocardial infarction rule-out for emergency department chest pain patients: the case of copeptin.

The evaluation of patients admitted at the emergency department (ED) for chest pain is challenging and involves many different clinical specialists including emergency physicians, laboratory professionals and cardiologists. The preferable approach to deal with this issue is to develop joint protocols that will assist the clinical decision-making to quickly and accurately rule-out patients with non life-threatening conditions that can be considered for early and safe discharge or further outpatient follow-up, rule-in patients with acute coronary syndrome and raise the degree of alert of the emergency physicians on non-cardiac life-threatening emergencies. The introduction of novel biomarkers alongside the well-established troponins might support this process and also provide prognostic information about acute short-term or chronic long-term risk and severity. Among the various biomarkers, copeptin measurement holds appealing perspectives. The utility of combining troponin with copeptin might be cost-effective due to the high negative predictive value of the latter biomarker in the rule-out of an acute coronary syndrome. Moreover, in the presence of a remarkably increased concentration (e.g., more than 10 times the upper limit of the reference range), to reveal the presence of acute life-threatening conditions that may not necessarily be identified with the use of troponin alone. The aim of this article is to review current evidence about the clinical significance of copeptin testing in the ED as well as its appropriate placing within diagnostic protocols