Ensayo clínico para determinar si el momento de administración del ácido tranexámico en la cirugía de prótesis total de rodilla con torniquete influye en el sangrado perioperatorio

Background and objectivesThe ideal timing of tranexamic acid administration in total knee arthroplasty with tourniquet remains unclear. Our primary objective was to prove if administering it before surgical incision, instead of before releasing the tourniquet, reduces postoperative bleeding. A second objective was to determine whether a second dose reduces post-operative bleeding.Material and methodsA prospective, double-blind clinical trial was performed on 212 patients scheduled for total knee arthroplasty. They were randomised into 4 groups. Tranexamic acid was administered before the surgical incision in “pre-induction groups” (1 and 2), and just before the tourniquet release in “pre-release groups” (3 and 4). Groups 2 and 4 received a second dose 3 hours post-surgery. Main outcome was postoperative bleeding (visible blood loss and calculated total bleeding). Secondary outcomes were haemoglobin variations, complications and transfusion rate.ResultsThe mean calculated total bleeding was 1563 ml (95%CI: 1445 to 1681) in preinduction groups versus 1576 ml (95%CI: 1439 to 1713) in pre-release groups (P = .9); 1579 ml (95%CI: 1452 to 1706) in single-dose groups versus 1559 ml (95%CI: 1431 to 1686) in double-dose groups (P = .82). One patient was transfused. The mean haemoglobin at discharge was 10.4 g/dl (95%CI: 10.2 to 10.7) in singledose groups versus 10.8 (95%CI: 10.6 to 11.1) in double-dose groups (P = .06).ConclusionsThere were no differences in bleeding or transfusion regarding the time of tranexamic acid administration. The second dose had not impact on outcomes.Trial registration: EudraCT 2016-000071-24.     

Neighborhood disadvantage,individual-level socioeconomic position and physical function: A cross-sectional multilevel analysis

IntroductionUnderstanding associations between physical function and neighborhood disadvantage may provide insights into which interventions might best contribute to reducing socioeconomic inequalities in health. This study examines associations between neighborhood-disadvantage, individual-level socioeconomic position (SEP) and physical function from a multilevel perspective.MethodsData were obtained from the HABITAT multilevel longitudinal (2007-13) study of middle-aged adults, using data from the fourth wave (2013). This investigation included 6004 residents (age 46–71 years) of 535 neighborhoods in Brisbane, Australia. Physical function was measured using the PF-10 (0–100), with higher scores indicating better function. The data were analyzed using multilevel linear regression and were extended to test for cross-level interactions by including interaction terms for different combinations of SEP (education, occupation, household income) and neighborhood disadvantage on physical function.ResultsResidents of the most disadvantaged neighborhoods reported significantly lower physical function (men: β − 11.36 95% CI − 13.74, − 8.99; women: β − 11.41 95% CI − 13.60, − 9.22). These associations remained after adjustment for individual-level SEP. Individuals with no post-school education, those permanently unable to work, and members of the lowest household income had significantly poorer physical function. Cross-level interactions suggested that the relationship between household income and physical function is different across levels of neighborhood disadvantage for men; and for education and occupation for women.ConclusionLiving in a disadvantaged neighborhood was negatively associated with physical function after adjustment for individual-level SEP. These results may assist in the development of policy-relevant targeted interventions to delay the rate of physical function decline at a community-level.     

Making the Cut: Perspectives on the Surgical Management of Infective Endocarditis Among People Who Use Intravenous Drugs

In this article we review the perspectives in the literature around surgical treatment for infective endocarditis (IE) in people who use intravenous drugs (PUID). PUID are at increased risk for IE; however, controversy exists regarding how to best manage these patients. We explore the outcomes for surgical treatment in PUID with IE, contrasting these with patients with IE who do not use drugs. We describe some of the perspectives in the literature around second valve replacement for PUID with IE, arguing that moralistic arguments are not on the basis of evidence and perpetuate the stigma experienced by PUID who seek treatment for IE. Finally, we explore the role of substance use interventions in the treatment of PUID with IE, and advocate for further evidence. PUID with IE are a highly stigmatized patient subgroup for whom best practice management strategies are not always implemented, emphasizing the need for further research and advocacy.     

Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.     

Curbing the tobacco epidemic: Employing behavioral strategies or rearranging the deckchairs on the Titanic?

Henningfield brilliantly dissected the deadly comprehensive tactics of the tobacco industry but Food and Drug Administration and WHO strategies against the tobacco epidemic must be questioned. The Food and Drug Administration has the authority to regulate tobacco production (2009 Tobacco Control Act) but fails to ban menthol and reduce cigarettes nicotine content. As little has changed, the Healthy People 2010 objective of reducing the prevalence of cigarette smoking among adults to 12% by 2010 in the US will be attained by 2030. The monitoring of the WHO Framework Convention on Tobacco Control (WHO FCTC) is passive, even when governments repeatedly violate the Article 5.3 of the Convention, which specifically requires protecting public policy from tobacco industry interference. Since 2004, the year after the adoption of the Convention, the prevalence of daily smoking has leveled off and the 2012 annualized rate of change in prevalence of daily smoking was almost null. This contrasts with a 2% annual decrease in the prevalence of daily smoking from 1980 to 2004. The tobacco endgame needs acts, not bureaucracies. Two counties have been moving forward, Brazil has banned menthol and Australia has implemented plain packaging.