Australian Football League concussion guidelines: what do community players think?

BACKGROUND: Preventing concussion in sport is a global challenge. To assess community-level adult male Australian Football players\u27 views on following the Australian Football League\u27s (AFL) concussion guidelines. METHODS: 3 focus groups, each comprising 6 players from 1 regional league, were conducted until saturation of issues raised. Discussions followed a semistructured script and were audio-recorded and transcribed verbatim. Thematic analysis was conducted by 2 coders independently. RESULTS: Identified advantages of the guidelines included highlighting the seriousness of concussion; changing the culture around playing with concussion and shifting return-to-play decision responsibility from players to others. Disadvantages included players being removed from play unnecessarily; removal of players\u27 rights to decide if they are fit to play and players changing their behaviours to avoid being removed from play. Identified facilitators to guideline use included local league enforcement; broad information dissemination and impartial medically trained staff to assess concussion. Identified barriers to guideline use included players\u27 desire to play at all costs; external pressure that encouraged players to return to play prematurely; and inconvenience and cost. CONCLUSIONS: Players generally understand that the AFL concussion guidelines protect their long-term welfare. However, their desire to play at all costs and help their team win is a common barrier to reporting concussion and adhering to guidelines. Leagues should take a lead role by mandating and enforcing the use of the guidelines and educating coaches, game day medical providers and players. The return-to-play component of the guidelines is complex and needs further consideration in the context of community sport

Phage display-based discovery of cyclic peptides against the broad spectrum bacterial anti-virulence target CsrA

Small macrocyclic peptides are promising candidates for new anti-infective drugs. To date, such peptides have been poorly studied in the context of anti-virulence targets. Using phage display and a self-designed peptide library, we identified a cyclic heptapeptide that can bind the carbon storage regulator A (CsrA) from Yersinia pseudotuberculosis and displace bound RNA. This disulfide-bridged peptide, showed an IC50 value in the low micromolar range. Upon further characterization, cyclisation was found to be essential for its activity. To increase metabolic stability, a series of disulfide mimetics were designed and a redox-stable 1,4-disubstituted 1,2,3-triazole analogue displayed activity in the double-digit micromolar range. Further experiments revealed that this triazole peptidomimetic is also active against CsrA from Escherichia coli and RsmA from Pseudomonas aeruginosa. This study provides an ideal starting point for medicinal chemistry optimization of this macrocyclic peptide and might pave the way towards broadacting virulence modulators

Red Oak Seedlings as Indicators of Deer Browse Pressure: Gauging the Outcome of Different White-Tailed Deer Management Approaches

After decades of high deer populations, North American forests have lost much of their previous biodiversity. Any landscape‐level recovery requires substantial reduc‐ tions in deer herds, but modern societies and wildlife management agencies appear unable to devise appropriate solutions to this chronic ecological and human health crisis. We evaluated the effectiveness of fertility control and hunting in reducing deer impacts at Cornell University. We estimated spring deer populations and planted Quercus rubra seedlings to assess deer browse pressure, rodent attack, and other factors compromising seedling performance. Oak seedlings protected in cages grew well, but deer annually browsed ≥60% of unprotected seedlings. Despite female ster‐ ilization rates of \u3e90%, the deer population remained stable. Neither sterilization nor recreational hunting reduced deer browse rates and neither appears able to achieve reductions in deer populations or their impacts. We eliminated deer sterilization and recreational hunting in a core management area in favor of allowing volunteer arch‐ ers to shoot deer over bait, including at night. This resulted in a substantial reduction in the deer population and a linear decline in browse rates as a function of spring deer abundance. Public trust stewardship of North American landscapes will require a fundamental overhaul in deer management to provide for a brighter future, and oak seedlings may be a promising metric to assess success. These changes will re‐ quire intense public debate and may require new approaches such as regulated com‐ mercial hunting, natural dispersal, or intentional release of important deer predators (e.g., wolves and mountain lions). Such drastic changes in deer management will be highly controversial, and at present, likely difficult to implement in North America. However, the future of our forest ecosystems and their associated biodiversity will depend on evidence to guide change in landscape management and stewardship

Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

Background: Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure. Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether–lumefantrine, artesunate–mefloquine, artesunate–amodiaquine, or dihydroartemisinin–piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2–3 and between day 0 and days 5–7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680. Findings: Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2–3 were –0·6 g/dL (95% CI –0·7 to –0·5), –0·7 g/dL (–0·8 to –0·5), –0·6 g/dL (–0·7 to –0·4), and –0·5 g/dL (–0·7 to –0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2–3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias. Interpretation: Treatment of patients with G6PD activity of 30% or higher with 0·25–0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25–1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses. Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Background: Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. Methods: For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether–lumefantrine, artesunate–mefloquine, artesunate–amodiaquine, or dihydroartemisinin–piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5–7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. Findings: Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2–53·9) in 1470 patients treated without primaquine, 19·3% (16·9–21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0–9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17–0·27; p<0·0001) and high-dose primaquine (0·10, 0·08–0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5–7 were reported by 4·0% (95% CI 0·0–8·7) of 893 patients treated without primaquine, 6·2% (0·5–12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8–10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7–16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. Interpretation: Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. Funding: Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Independent appraiser assessment of the quality, methodological rigour and transparency of the development of the 2008 international consensus statement on concussion in sport

AIM: In recent years, considerable effort has been devoted to the development and revisions to an international consensus statement on concussion in sport (ICSCS). The aim of this study was to obtain expert views on the methodological rigour and transparency with which the 2008 ICSCS was developed, as a precursor to the development of the 2012 update. METHODS: Delegates registered for the 2012 fourth International Conference on Concussion in Sport, selected local concussion researchers not involved in any prior international consensus meetings, and all authors of the 2008 ICSCS published paper were invited to assess the methodological rigour and transparency with which the 2008 ICSCS was developed. The online Appraisal of Guidelines for Research and Evaluation (AGREE) II assessment tool, with six quality domains, was used and domain scores were expressed as a percentage of the maximum possible score for that domain. RESULTS: 18 appraisers completed the online AGREE II assessment. Ten appraisers said they would recommend the 2008 ICSCS for use (without modification) and seven said they would recommend its use with some modification. The \u27scope and purpose\u27 and \u27clarity of presentation\u27 were rated highest, both scoring 78%. The lowest scoring domain was \u27applicability\u27 with a score of 55%. CONCLUSIONS: The quality of the ICSCS is important because it is used to guide return-to-play decisions and the management of sport-related concussions. This appraisal of the 2008 ICSCS suggests that a greater focus is needed on the actual implementation of future ICSCS and the relationship between implementation and desired health outcomes

Ensuring implementation success : how should coach injury prevention education be improved if we want coaches to deliver safety programmes during training sessions?

Coaches play a major role in encouraging and ensuring that participants of their teams adopt appropriate safety practices. However, the extent to which the coaches undertake this role will depend upon their attitudes about injury prevention, their perceptions of what the other coaches usually do and their own beliefs about how much control they have in delivering such programmes. Fifty-one junior netball coaches were surveyed about incorporating the teaching of correct (safe) landing technique during their delivery of training sessions to junior players. Overall, >94% of coaches had strongly positive attitudes towards teaching correct landing technique and >80% had strongly positive perceptions of their own control over delivering such programmes. Coaches’ ratings of social norms relating to what others think about teaching safe landing were more positive (>94%) than those relating to what others actually do (63–74%). In conclusion, the junior coaches were generally receptive towards delivering safe landing training programmes in the training sessions they led. Future coach education could include role modelling by prominent coaches so that more community-level coaches are aware that this is a behaviour that many coaches can, and do, engage in

Encouraging junior community netball players to learn correct safe landing technique

Abstract not availablePeta E. White, Shahid Ullah, Alex Donaldson, Leonie Otago, Natalie Saunders, Maria Romiti, Caroline F. Finc