Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Nouveaux règlemens pour l'administration de la justice, avec les tarifs des droits dûs aux officiers de justice pour leurs frais et salaires, et la taxe des dépens de tous les procès. 3e éd.. Edition 3,Tome 1

[Acte royal]

Nouveaux règlemens pour l'administration de la justice, avec les tarifs des droits dûs aux officiers de justice pour leurs frais et salaires, et la taxe des dépens de tous les procès. 3e éd.. Edition 3,Tome 2

[Acte royal]

Tobacco and tuberculosis

Smoking is not only the most important source of avoidable disability and death, but a risk factor for TB infection, disease and death. Even passive smoking exposure may increase the risk of infection and disease in adults and children exposed to TB. Considering the increase in tobacco consumption in developing countries, where the prevalence of TB is the highest, smoking may be responsible for a large part of the burden of disease. Therefore, medical advice and counselling in smoking cessation is an important activity for all care providers engaged in management of TB

Implementation of the Federal Highway Administration Final Rule on Work Zone Safety and Mobility, 2007

The Federal Highway Administration published the final rule updating 23 CFR 630 Subpart J in September 2004. The revised rule requires agencies using federal funding to address both safety and mobility in planning and construction of roadway improvements. The Iowa Department of Transportation (Iowa DOT) requested the assistance of the Center for Transportation and Research in developing guidance for a policy and procedures to comply with the final rule. This report describes an in-depth examination of current Iowa DOT project development processes for all types of improvements, including maintenance, as well as a detailed characterization of work zone impact considerations throughout project completion. To comply with both the letter and perceived intent of the final rule on safety and mobility, the report features a suggested work zone policy statement and suggested revisions in the Iowa DOT project development processes, including a definition of the key element: significant projects.

Latent tuberculosis: which test in which situation?

Detection of latent tuberculosis infection (LTBI) is a cost-effective procedure in patients at high risk of developing tuberculosis later and who could benefit from preventive treatment. The commonest situation where screening is indicated is the search for infected contacts of an index case with pulmonary tuberculosis. As a screening procedure the current tendency is to replace the time-honoured tuberculin skin test by one of the new blood tests measuring the release of interferon gamma by sensitised T lymphocytes after stimulation by specific peptides from M. tuberculosis. The main advantage of the new tests is the absence of interference with BCG and non-tuberculous mycobacteria, which confers high specificity on the test. This allows a more selective choice of persons for whom preventive treatment is indicated. Some controversial issues remain, such as sensitivity in children and immunocompromised subjects, the predictive value of the blood test and interpretation of possible changes in test results over time. The technical aspects required for performance of the tests must be considered.

Clinical studies of experimental vaccines.

PURPOSE OF REVIEW: The scope of this review is to provide the current status of HIV vaccine clinical development. A series of issues regarding the type of immune response stimulated by the candidate vaccines in the pipeline, the advances in the immune correlates of protection, the need for an effective decision-making process for selection of candidate vaccines into further clinical development and the rationale for clinical trials will also be discussed. RECENT FINDINGS: Efforts in the development of HIV vaccines inducing broad neutralizing antibodies have failed so far. The current pipeline is predominantly composed of candidate vaccines designed to induce cellular immunity and particularly T-cell response. For these reasons, these candidate vaccines have been termed 'T-cell vaccines'. A large number of candidate vaccines or vaccine combinations have entered phase I-II clinical trials in 2005. Furthermore, an adenovirus vector-based vaccine has entered proof-of-concept efficacy trial and a canarypox vector in combination with a protein-based vaccine is currently being evaluated in phase III clinical trials. T-cell vaccines have been shown to be safe and the most recent generation of these vaccines also has substantial immunogenicity. SUMMARY: Only clinical trials can provide the definitive answer to immune correlates of protection and vaccine efficacy.

Report on a review of selected general and application controls over the Iowa Public Employees’ Retirement System (IPERS) I-QUE Pension Administration System for the period April 9, 2015 through May 7, 2015

Report on a review of selected general and application controls over the Iowa Public Employees’ Retirement System (IPERS) I-QUE Pension Administration System for the period April 9, 2015 through May 7, 2015

Iowa Tuberculosis Control Program 2014 Annual Report

This report provides a summary of Tuberculosis (TB) in Iowa and the activities and achievements of the TB Control Program and our partners during the 2014 calendar year. This report provides Iowa-specific TB rates, funding sources, and program-specific data, often in ten-year time lines to more accurately reflect trends. Previous reports included TB control efforts by the World Health Organization and the Centers for Disease Control and Prevention. Reports paid tribute to the role TB disease played in the history of man including historical TB treatments, myths, and bygone TB control practices. The 2014 Report does not include these overviews. Please refer to previous reports for this information. The annual report serves as an informational resource for stakeholders, local partners, policy makers and others interested in Iowa’s TB Control efforts.

Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4(+) TÂ cells in active disease.

Protective immunity to Mycobacterium tuberculosis (Mtb) is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized Mtb-specific CD4(+) T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent Mtb infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL-17A, IFN-γ, TNF-α, and IL-2 by Mtb-specific CD4(+) T cells was assessed both directly ex vivo and following in vitro antigen-specific T-cell expansion. Unlike for extracellular bacteria, Mtb-specific CD4(+) T-cell responses lacked immediate ex vivo IL-17A effector function in both LTBI and TB individuals. Furthermore, Mtb-specific Th17 cells were absent in BALs, while extracellular bacteria-specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only Mtb-specific CD4(+) T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL-17A following Mtb-specific T-cell expansion. Finally, IL-17A acquisition by Mtb-specific CD4(+) T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that Mtb-specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.