The predictive value of the heart rate variability‐derived Analgesia Nociception Index in children anaesthetized with sevoflurane: An observational pilot study

Background

The heart rate variability (HRV)‐derived Analgesia Nociception Index (ANI?) is a continuous noninvasive tool to assess the nociception/antinociception balance in unconscious patients. It has been shown to be superior to haemodynamic variables in detecting insufficient antinociception in children, while little is known about its predictive value.

Methods

The primary objective of this prospective observational pilot study in paediatric surgical patients under sevoflurane anaesthesia was to compare the predictive value of the ANI and heart rate to help decide to give additional opioids. The paediatric anaesthesiologist in charge was blinded to ANI values.

Results

In patients with an ANI value <50 (indicating insufficient antinociception) at the moment of decision, ANI values dropped from ±55 (indicating sufficient antinociception) to ±35, starting 60 s before decision. Within 120 s after administration of fentanyl (1 μg/kg), ANI values returned to ±60. This phenomenon was only observed in the ANI values derived from HRV data averaged over 2 min. Heart rate remained unchanged. In patients with ANI values ≥50 at the time of decision, opioid administration had no effect on ANI or heart rate. The same accounts for morphine for postoperative analgesia and fentanyl in case of intraoperative movement.

Conclusions

This study provides evidence of a better predictive value of the ANI in detecting insufficient antinociception in paediatric surgical patients than heart rate. The same accounts for depicting re‐establishment of sufficient antinociception after opioid drug administration.

Significance

In paediatric surgical patients anaesthetized with sevoflurane, the heart rate variability‐derived Analgesia Nociception Index (ANI) appears to be a better predictor of insufficient antinociception than heart rate. The ANI also appears to depict re‐establishment of sufficient antinociception better than heart rate.

     

HIV-related conspiracy beliefs and its relationships with HIV testing and unprotected sex among men who have sex with men in Tshwane (Pretoria), South Africa

The objective of this study was to determine extent of HIV conspiracy belief endorsement among men who have sex with men (MSM) in Pretoria, and assess whether endorsement of HIV conspiracy beliefs are associated with inconsistent condom use and never testing for HIV. A cross-sectional survey using respondent-driven sampling was conducted between February and August 2009. A high proportion of respondents endorsed HIV conspiracy beliefs. MSM commonly endorsed beliefs related to AIDS information being held back from the general public (51.0%), HIV being a man-made virus (25.5%), and people being used as guinea pigs in HIV research and with HIV treatments (approximately 20%). Bisexually- or heterosexually-identified MSM were significantly more likely to endorse conspiracy beliefs compared to homosexually-identified MSM (38.5% vs. 14.7%). Endorsing conspiracy beliefs was not associated with unprotected anal intercourse; however, it was significantly associated with not having been HIV tested (AOR: 2.4; 95% CI: 1.1-5.7). Endorsing beliefs in HIV conspiracies reflects a mistrust in government institutions and systems which could be an impediment to seeking HIV-related services, including HIV counseling and testing.     

Improved method for the generation and selection of homogeneous lumpy skin disease virus (SA-Neethling) recombinants

Lumpy skin disease virus (LSDV) is being developed as a vector for recombinant vaccines against diseases of veterinary importance. A strategy for generating viral thymidine kinase (TK) gene-disrupted recombinants which are stable and homogeneous using the South African Neethling vaccine strain of LSDV as vector has been developed. To assist with the selection process, the Escherichia coli beta-galactosidase (lacZ) visual marker gene was incorporated into the constructs. However, the use of lacZ has certain limitations. An improved strategy was then devised substituting lacZ with the enhanced green fluorescent protein (EGFP) under control of the vaccinia virus (VV) P11K late promoter. The EGFP marker was found to enhance the selection process, and with the inclusion of additional sonication and filtration steps the number of passages required to select recombinants to homogeneity has been reduced. In support of the improved method for generation and selection of recombinants described, three different LSDV recombinants expressing the glycoprotein genes of bovine ephemeral fever virus, Rift Valley fever virus and rabies virus were prepared and characterised.     

The Role of Waste Management in Control of Rabies: A Neglected Issue

Despite being vaccine preventable, the global burden of dog rabies remains significant, and historically it is the rural and marginalized communities in developing countries of Africa and Asia that are most threatened by the disease. In recent years, the developing world has been experiencing unprecedented increases in urbanization, with a correspondingly massive increase in municipal solid waste generation, among other things. Inefficient and inadequate waste collection and management, due to lack of resources and planning, led to significant increases in the volumes of waste on the streets and in open dumps, where it serves as food sources for free-roaming dogs. In this commentary, we discuss examples of poor waste management and the likely impact on rabies control efforts through the sustenance of free-roaming dogs in some dog rabies-endemic countries. We aim to stress the importance of implementing strategies that effectively address this particular issue as an important component of humane dog population management, as it relates to aspirations for the control and elimination of dog rabies per se.     

Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers—using a novel selection method—were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.     

Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura

To investigate whether altered megakaryocyte morphology contributes to reduced platelet production in idiopathic thrombocytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was performed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apoptosis were present in 78% +/- 14% of ITP megakaryocytes, which could be reversed by in vivo treatment with prednisone and intravenous immunoglobulin. Immunohistochemistry of bone marrow biopsies of ITP patients with extensive apoptosis showed an increased number of megakaryocytes with activated caspase-3 compared with normal (28% +/- 4% versus 0%). No difference, however, was observed in the number of bone marrow megakaryocyte colony-forming units (ITP, 118 +/- 93/105 bone marrow cells; versus controls, 128 +/- 101/105 bone marrow cells; P =.7). To demonstrate that circulating antibodies might affect megakaryocytes, suspension cultures of CD34+ cells were performed with ITP or normal plasma. Morphology compatible with (para-)apoptosis could be induced in cultured megakaryocytes with ITP plasma (2 of 10 samples positive for antiplatelet autoantibodies). Finally, the plasma glycocalicin index, a parameter of platelet and megakaryocyte destruction, was increased in ITP (57 +/- 70 versus 0.7 +/- 0.2; P =.009) and correlated with the proportion of megakaryocytes showing (para-) apoptotic ultrastructure (P =.02; r = 0.7). In conclusion, most ITP megakaryocytes show ultrastructural features of (para-) apoptosis, probably due to action of factors present in ITP plasma.     

Developing the “120 by 20” Goal for the Global FP2020 Initiative

This report describes the purpose for developing a quantitative goal for the London Summit on Family Planning held in July 2012, the methodology behind its formulation, and the lessons learned in the process. The London Summit has evolved into the global initiative known as FP2020, and the goal has become “120 by 20,” or reaching 120 million additional users of modern contraceptive methods by 2020 in the world's poorest countries. The success of FP2020 will first be evaluated on the basis of quantitative verification to determine that the “120 by 20” goal was reached. More important, however, is the extent to which the goal today serves as a global rallying cry to mobilize resources and leadership around current family planning programs, with a focus on voluntary family planning and quality of care, and with an emphasis on meeting girls' and women's unmet needs and their right to practice contraception. We hope this article provides greater transparency and understanding of the FP2020 goal, and that the global goal spurs annual monitoring of progress toward national goals in the world's poorest countries.