Kelp Morphology and Herbivory are Maintained Across Latitude Despite Geographic Shift in Kelp-wounding Herbivores

Herbivores can drastically alter the morphology of macroalgae by directly consuming tissue and by inflicting structural wounds. Wounds can result in large amounts of tissue breaking away from macroalgae, amplifying the damage initially caused by herbivores. Herbivores that commonly wound macroalgae often occur over only a portion of a macroalga’s lifespan or geographic range. However, we know little about the influence of these periodic or regional occurrences of herbivores on the large-scale seasonal and geographical patterns of macroalgal morphology. We used the intertidal kelp Egregia menziesii to investigate how the kelp’s morphology and the prevalence of two prominent kelp-wounding herbivores (limpets and amphipods) changed over two seasons (spring and summer) and over the northern extent of the kelp’s geographic range (six sites from central California to northern Washington). Wounds from limpets and amphipods often result in the kelp’s fronds being pruned (intercalary meristem broken away), so we quantified kelp size (combined length of all fronds) and pruning (proportion of broken fronds). We found similar results in each season: herbivores were most likely to occur on large, pruned kelp regardless of site; and limpets were the dominant herbivore at southern sites, while amphipods were dominant at northern sites. Despite the geographic shift in the dominant herbivore, kelp had similar levels of total herbivore prevalence (limpets and/or amphipods) and similar morphologies across sites. Our results suggest that large-scale geographic similarities in macroalgal wounding, despite regional variation in the herbivore community, can maintain similar macroalgal morphologies over large geographic areas

Low influenza vaccine uptake by healthcare workers caring for the elderly in South African old age homes and primary healthcare facilities

Background: The elderly bear the highest burden of South Africa’s estimated annual >10 million influenza cases and >11,000 influenza-related deaths. Unvaccinated healthcare workers (HCWs) are at high occupational risk of contracting influenza, and may transmit influenza to elderly patients in their care. Thus, the South African National Department of Health recommends that HCWs receive annual influenza vaccination. This study aimed to determine influenza vaccination coverage among HCWs; identify reasons for their vaccination status; and investigate if HCWs recommend vaccination to their elderly patients. Methods: A descriptive study was conducted in 18 community health centres and 44 private sector and non-governmental organisation managed old age homes across South Africa, using a self-administered structured questionnaire, which was distributed to 360 HCWs present on the day of data collection. Data were captured using Microsoft ExcelTM and imported to Epi InfoTM 7 (Centers for Disease Control and Prevention, USA) for descriptive statistical analysis. Ethics approval (SMUREC/P/36/2018: PG) and permission to conduct the study at the facilities were obtained. All participants provided informed consent. Results: The response rate was 76.7% (276/360). Most participants were female (90.9% [251/276]), nursing professionals (81.2% [224/276]) with a mean age of 41.1 ± 11.7 years. Although 62.7% of participants indicated having ever received at least one dose of the influenza vaccine, influenza vaccine uptake for 2017 and 2018 was 24.36% (41/276) and 33.3% (92/276) respectively. The main reasons given for never being vaccinated against influenza were related to the unavailability of the vaccine (70.9%) and vaccine hesitancy (27.2%). Most participants (67.8% [187/276]) recommended vaccines to elderly patients in their care. Conclusion: The main reasons behind low influenza vaccine uptake by HCWs in South Africa who care for the elderly were related to unavailability of the vaccine and vaccine hesitancy. Strategies to educate HCWs on the importance of influenza vaccination, while concurrently increasing sustained and easy access to the vaccine by HCWs are needed to preserve public health

A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3-internal tandem duplication mutations, 23% FLT3–tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively

Contextualised strategies to increase childhood and adolescent vaccination coverage in South Africa : a mixed-methods study

CITATION: Wiysonge, Charles Shey et al. 2020. Contextualised strategies to increase childhood and adolescent vaccination coverage in South Africa : a mixed-methods study. BMJ Open, 10 (6):e028476, doi:10.1136/bmjopen-2018-028476.The original publication is available at: https://bmjopen.bmj.comIntroduction Despite the unparalleled success of immunisation in the control of vaccine preventable diseases, immunisation coverage in South Africa remains suboptimal. While many evidence-based interventions have successfully improved vaccination coverage in other countries, they are not necessarily appropriate to the immunisation needs, barriers and facilitators of South Africa. The aim of this research is to investigate barriers and facilitators to optimal vaccination uptake, and develop contextualised strategies and implementation plans to increase childhood and adolescent vaccination coverage in South Africa. Methods The study will employ a mixed-methods research design. It will be conducted over three iterative phases and use the Adopt, Contextualise or Adapt (ACA) model as an overarching conceptual framework. Phase 1 will identify, and develop a sampling frame of, immunisation stakeholders involved in the design, planning and implementation of childhood and human papillomavirus immunisation programmes in South Africa. Phase 2 will identify the main barriers and facilitators to, and solutions for, increasing vaccination coverage. This phase will comprise exploratory qualitative research with stakeholders and a review of existing systematic reviews on interventions for improving vaccination coverage. Using the findings from Phase 2 and the ACA model, Phase 3 will develop a set of proposed interventions and implementation action plans for improving immunisation coverage in South Africa. These plans will be discussed, revised and finalised through a series of participatory stakeholder workshops and an online questionnaire, conducted as part of Phase 3.Publisher's versio

Impact of lamivudine-based antiretroviral treatment on hepatitis B viremia in HIV-coinfected South Africans

This prospective study investigated the impact of lamivudine-containing antiretroviral therapy (ART) on HIV-positive patients in South Africa with baseline hepatitis B virus (HBV) infection. Follow-up samples from 56 HBV/HIV co-infected patients, 25 with occult HBV infection (OBI) and 31 with chronic HBV infection (CHB), were available for analysis. HBV viral loads were quantified at 6, 12, 18, and 24 months post-ART initiation by the COBAS TaqMan HBV Test 48 assay, and the HBV polymerase gene was amplified with an in-house nested polymerase chain reaction assay. During 24 months of lamivudine-based ART, 6 of 8 (75%) OBI and 4 of 6 (67%) CHB patients achieved undetectable levels of HBV DNA, while 2 patients had persistent HBV DNA levels 2 105 despite lamivudine-based ART for 24 months. HIV viremia was undetectable in all patients at 12 months, suggesting high adherence to ART. Several lamivudine-associated HBV resistance mutations, including L180M, A181T, M204I, and M204V, were observed. Sequence analysis also revealed a rare genotype G infection. While resource-limited settings may use lamivudine-based ART because of availability and low cost, antivirals with dual therapy against HBV and HIV (e.g., lamivudine and tenofovir) should always be recommended with the regular monitoring of HBV viremia levels.The South African National Research Foundation, Poliomyelitis Research Foundation, Stella and Paul Lowenstein Trust, and Canon and Collins scholarship.http://www.mdpi.com/journal/virusesam2021Medical Virolog

Prognostic impact of <i>CEBPA </i>mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIP ms). (Figure presented.)</p

Prognostic impact of CEBPA mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms)

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Human papillomavirus vaccine hesitancy highly evident among caregivers of girls attending South African private schools

The viral spread of social media misinformation and disinformation regarding human papillomavirus (HPV) vaccination safety has resulted in widespread vaccine hesitancy and suboptimal HPV vaccination uptake. We previously reported that only 19.4% of age-eligible private school girls in South Africa in 2018 had received ≥1 HPV vaccine dose. Here, we report on reasons given by caregivers for why their daughters were unvaccinated. An online survey targeting caregivers of girls in grades 4–7 attending South African private schools was conducted. Caregivers of unvaccinated girls provided the most important reason for their daughter not being vaccinated by either selecting from a list of coded reasons or providing a free text reason. Free text reasons were analysed, coded and added to the list of coded reasons, which were categorised according to broad themes. Frequency distributions of reasons and categories were calculated. Most reasons were related to vaccine hesitancy (61.4%), followed by lack of access to the vaccine (21.3%) and lack of information (15.7%). HPV vaccination coverage among age-eligible girls can be improved by including private-sector schools in the South African HPV vaccination programme, training healthcare providers to advocate for HPV vaccination and extending HPV vaccination advocacy campaigns to include private-sector educators