A multimedia consent tool for research participants in the Gambia: a randomized controlled trial

ObjectiveTo assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.MethodsAdults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants’ comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7, 14, 21 and 28). The acceptability and ease of use of the multimedia tool were assessed in focus groups.FindingsOn day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P = 0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence interval, CI: 0.12–0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13–0.82). There was no significant independent association with educational level. The risk that a participant’s comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22, 95% CI: 0.16–0.31). Overall, 70% (42/60) of focus group participants from the intervention arm found the multimedia tool clear and easy to understand.ConclusionA multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy.     

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study

Background

There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx.

Methods

A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines.

Results

A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus, 27.8% H. influenzae. Carriage of H. influenzae (OR = 0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR = 0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage.

Conclusions

Nasopharyngeal bacterial carriage is unaffected by DTP-Hib-HepB vaccination and reduced after measles-yellow fever vaccination.     

Ebola Risk Perception in Germany, 2014

Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.     

Type A dissection following endovascular thoracic aortic stent-graft repair.

PURPOSE: To describe our experience with endovascular stent-graft repairs in the thoracic aorta focusing on the secondary complication of type A dissection. METHODS: Between January 1996 and April 2004, 73 patients were treated for traumatic thoracic aortic rupture (n=15), type B dissection (n=22), or atherosclerotic descending thoracic aortic aneurysms (TAA, n=36). A retrospective review of the records found 5 (6.8%) patients (3 men; median age 64 years, range 43-87) who experienced a type A dissection at a median 20 days (range 2-124) after thoracic stent-graft repair for 3 type B dissections, 1 TAA, and a late type I endoleak that appeared 28 months after initial stent-graft repair of a traumatic dissection. RESULTS: In 3 patients (2 dissections, 1 endoleak), a tear in the aortic wall at the proximal stent-graft was responsible for a retrograde type A dissection. Underlying disease was the cause of the type A dissection in the 2 other patients (1 dissection, 1 TAA) and was unrelated to the stent-grafts. Three patients underwent open surgery at 3, 26, and 124 days after stent-graft placement; 2 procedures were successful, but the third patient died 3 months later due to multiorgan failure. Two type A dissections were untreated: one patient died from cardiac tamponade 14 days after successful stent-graft exclusion of the type I endoleak; the other patient refused further treatment and survived. The procedure-related mortality following acute retrograde type A dissection was 40%. CONCLUSIONS: Endovascular stent-graft repair of the thoracic aorta is associated with lower morbidity and mortality rates than surgical repair, although potentially lethal complications, acute or delayed, may occur.     

CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> Regulatory T Cells Have Divergent Effects on Intestinal Inflammation in IL-10 Gene-Deficient Mice

The regulatory effect of murine CD4⁺CD25⁺ T-cells in vivo appears to be dependent on the secretion of IL-10. The lack of IL-10 in the IL-10 gene-deficient mouse has a profoundly negative effect on the mouse’s regulation of the response to intestinal bacteria, resulting in severe enterocolitis. We investigated the effect of neonatal injection with wild-type CD4⁺CD25⁺ T-cells on the intestinal immune response in IL-10 gene-deficient mice. At the time of analysis, 8–15 weeks later, all mice demonstrated an increased, antigen-stimulated systemic response. However, the intestinal response was divergent with about half of the mice developing an intestinal inflammation with a high injury score, the other half demonstrating a remarkable reduction in injury score with a marked decrease in intestinal IFNγ release. Our data demonstrate that CD4⁺CD25⁺ T-cells can be activated in IL-10 gene-deficient mice and that this stimulation under stringent conditions has the potential to reduce intestinal inflammation.     

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.     

High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group

BackgroundKnowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.MethodsWe analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).ResultsSpinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.ConclusionsThe majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.     

Effects of 3D image-guided brachytherapy compared to 2D conventional brachytherapy on clinical outcomes in patients with cervical cancer: A systematic review and meta-analyses

PURPOSETo assess the effects of three-dimensional image-guided brachytherapy (3D BT) compared to bi-dimensional BT (2D BT) on clinical outcomes in patients with cervical cancer.METHODS AND MATERIALSWe searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL, Web of Science, and LILACS for studies assessing the effects of 3D BT versus 2D BT on clinical outcomes. Two reviewers independently screened retrieved citations, extracted data and assessed risk of bias from eligible studies. Hazard ratios (HR) were calculated from Kaplan-Meier curves considering the number of events, their timing and the followup of censored patients. We conducted meta-analyses of HR using the inverse-variance random-effects method. Risk Difference (RD) for toxicities were pooled using the Mantel–Haenszel random-effects method. We used the GRADE system to rate the certainty of evidence.RESULTSTwenty observational studies involving 4287 patients were included. The meta-analyses assessing the effect of 3D BT versus 2D BT on overall survival resulted in a HR of 0.78 (95%CI 0.62–0.98), HR of 0.75 (95%CI 0.62–0.90) for pelvic disease-free survival, HR of 0.93 (95%CI 0.81–1.06) for metastatic disease-free survival, and HR of 0.77 (95%CI 0.59–0.99) for local control. Grade 3–4 global and gastrointestinal toxicities were, respectively, 9% lower (95%CI 6% to 11%) and 5% lower (95%CI 2% to 8%) in patients receiving 3D BT versus 2D BT. Certainty of evidence was very low for all assessed outcomes.CONCLUSIONSOur study may suggest a benefit of 3D BT over conventional 2D BT on important clinical outcomes.