Media reporting of tenofovir trials in Cambodia and Cameroon

BACKGROUND: Two planned trials of pre-exposure prophylaxis tenofovir in Cambodia and Cameroon to prevent HIV infection in high-risk populations were closed due to activist pressure on host country governments. The international news media contributed substantially as the primary source of knowledge transfer regarding the trials. We aimed to characterize the nature of reporting, specifically focusing on the issues identified by media reports regarding each trial. METHODS: With the aid of an information specialist, we searched 3 electronic media databases, 5 electronic medical databases and extensively searched the Internet. In addition we contacted stakeholder groups. We included media reports addressing the trial closures, the reasons for the trial closures, and who was interviewed. We extracted data using content analysis independently, in duplicate. RESULTS: We included 24 reports on the Cambodian trial closure and 13 reports on the Cameroon trial closure. One academic news account incorrectly reported that it was an HIV vaccine trial that closed early. The primary reasons cited for the Cambodian trial closure were: a lack of medical insurance for trial related injuries (71%); human rights considerations (71%); study protocol concerns (46%); general suspicions regarding trial location (37%) and inadequate prevention counseling (29%). The primary reasons cited for the Cameroon trial closure were: inadequate access to care for seroconverters (69%); participants not sufficiently informed of risks (69%); inadequate number of staff (46%); participants being exploited (46%) and an unethical study design (38%). Only 3/23 (13%) reports acknowledged interviewing research personnel regarding the Cambodian trial, while 4/13 (30.8%) reports interviewed researchers involved in the Cameroon trial. CONCLUSION: Our review indicates that the issues addressed and validity of the media reports of these trials is highly variable. Given the potential impact of the media in formulation of health policy related to HIV, efforts are needed to effectively engage the media during periods of controversy in the HIV/AIDS epidemic

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Are Hindfoot Procedures More Painful than Forefoot – A Prospective Cohort Study in Foot and Ankle Reconstructive Surgery?

Category: Other Introduction/Purpose: Several variables are thought to have an effect on the post-operative pain relief after reconstructive foot and ankle surgery. In the past decade, the role of regional nerve blocks in the management of post-operative pain has become established. The technique(s) of regional blocks varies between centers and the published literature on this subject is inconsistent. More recently, image guided regional nerve blocks for post-op pain relief in F&A surgery have gained popularity. Traditionally, hindfoot reconstructive procedures are deemed to be more painful than the surgery involving the rest of the foot. This prospective study was carried out to examine this question. Methods: 143 patients undergoing elective foot and ankle surgery were prospectively studied. In addition to the demographics, the details of the anaesthetic used were also recorded. 70 patients received peripheral nerve blockade with guidance either by a nerve stimulator or ultrasonography. The procedures were categorised into those belonging to the forefoot, midfoot, hindfoot or combined. The magnitude of pain was recorded immediately post-operatively, at 6 hours and at 24 hours after the surgery, using the visual analog scale (VAS, 0 as ‘no pain’ and 10 as ‘ the worst possible pain’). All adverse effects were recorded. The patients’ satisfaction at two weeks after surgery was also assessed. Kruskal-Wallis test was used to perform non-parametric analysis between the groups. For categorical data, Pearson’s Chi-square test was used. Significant difference was demonstrated by a p-value < 0.05. Results: There was no difference in post-operative, 6 hours or 24 hours VAS in the patients having the hindfoot surgery or those having surgery involving the rest of the foot. Although patients who underwent peripheral nerve block had a satisfactory initial pain relief, they experienced significantly more pain at 24 hours than those who did not have a block (Table 1). There was no significant difference in the hospital stay or patient satisfaction at two weeks. In total, 94% patients were satisfied with their anaesthetic and would not mind having it again. Conclusion: This study provides evidence that contrary to the popular belief, hindfoot surgery is not more painful than the surgery involving the rest of the foot. Our results showed that patients who received peripheral nerve block probably had rebound pain at 24 hours after the surgery. Further studies are needed to explore this relationship. The detailed information provided by this study about the mean (and SD) VAS at various time points after surgery can be used to predict post-operative pain based on various pre-operative surgical and anaesthetic parameters

Disease Control

This item was digitized as part of the Million Books Project led by Carnegie Mellon University and supported by grants from the National Science Foundation (NSF). Cornell University coordinated the participation of land-grant and agricultural libraries in providing historical agricultural information for the digitization project; the University of Arizona Libraries, the College of Agriculture and Life Sciences, and the Office of Arid Lands Studies collaborated in the selection and provision of material for the digitization project.1. Diseases Cause Cotton Losses 2. Physiology Growth Survival and Parasites of Verticillium Wilt 3. Isolation of Biochemical and/or Morphological Characters Related to Tolerance to Verticillium Wilt in the Genus Gossypium 4. Soil Fumigation for Control of Verticillium Wilt 5. Disease Complex Studies 6. Cropping Sequences & Nitrogen Fertilization in Relation to Verticillium Wilt 7. The Effect of Phymatotrichum Root Rot of Cotton on Crop Residues 8. Nature of Resistence to Phymatotrichum omnivorum (Cotton Root Rot) 9. Evaluation of Soil Fumigants for Control of Cotton Root-Knot Nematodes Attacking Irrigated Cotton 10. Nematode Control 11. Deep Placement Fumigation for Root-Knot Nematode Control 12. Seedling Disease Control 13. Southwestern Cotton Rus

Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Background: Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity. Methods: PRISM was an open-label, randomised, phase 3 trial done at 70 hospitals across six countries. Patients aged 50 years or older who were undergoing elective major open abdominal surgery were randomly assigned (1:1) to receive CPAP within 4 h of the end of surgery or usual postoperative care. Patients were randomly assigned using a computer-generated minimisation algorithm with inbuilt concealment. The primary outcome was a composite of pneumonia, endotracheal re-intubation, or death within 30 days after randomisation, assessed in the intention-to-treat population. Safety was assessed in all patients who received CPAP. The trial is registered with the ISRCTN registry, ISRCTN56012545. Findings: Between Feb 8, 2016, and Nov 11, 2019, 4806 patients were randomly assigned (2405 to the CPAP group and 2401 to the usual care group), of whom 4793 were included in the primary analysis (2396 in the CPAP group and 2397 in the usual care group). 195 (8\ub71%) of 2396 patients in the CPAP group and 197 (8\ub72%) of 2397 patients in the usual care group met the composite primary outcome (adjusted odds ratio 1\ub701 [95% CI 0\ub781-1\ub724]; p=0\ub795). 200 (8\ub79%) of 2241 patients in the CPAP group had adverse events. The most common adverse events were claustrophobia (78 [3\ub75%] of 2241 patients), oronasal dryness (43 [1\ub79%]), excessive air leak (36 [1\ub76%]), vomiting (26 [1\ub72%]), and pain (24 [1\ub71%]). There were two serious adverse events: one patient had significant hearing loss and one patient had obstruction of their venous catheter caused by a CPAP hood, which resulted in transient haemodynamic instability. Interpretation: In this large clinical effectiveness trial, CPAP did not reduce the incidence of pneumonia, endotracheal re-intubation, or death after major abdominal surgery. Although CPAP has an important role in the treatment of respiratory failure after surgery, routine use of prophylactic post-operative CPAP is not recommended