Drug-free holidays: Compliance, tolerability, and acceptability of a 3-day atovaquone/proguanil schedule for pre-travel malaria chemoprophylaxis in Australian travellers

Background Poor compliance with chemoprophylaxis is a major contributing factor to the risk of malaria in travellers. Pre-travel chemoprophylaxis may improve compliance by enabling ‘drug-free holidays’. The standard treatment dose of atovaquone/proguanil (250mg/100mg, 4 tablets/day for 3 days) provides protection against malaria for at least 4 weeks, and could therefore potentially be used for pre-travel chemoprophylaxis. In this study, we assessed the compliance, tolerability, and acceptability of the 3-day atovaquone/proguanil schedule for malarial chemoprophylaxis. Methods 233 participants were recruited from four specialised travel medicine clinics in Australia. Adults travelling to malaria-endemic areas with low/medium risk for ≤4 weeks were enrolled, and prescribed the 3-day schedule of atovaquone/proguanil, completed at least one day before departure. Questionnaires were used to collect data on demographics, travel destination, medication compliance, side effects, and reasons for choosing the 3-day schedule. The study was registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12616000640404 Results Overall, 97.7% of participants complied with the 3-day schedule. Although side effects were reported in 43.3% of the participants, these were well tolerated, and mainly occurred during the first and second day. None of the participants developed malaria. The main reasons for choosing the 3-day schedule over standard chemoprophylaxis options were that it was easier to remember (72.1%), required taking fewer tablets (54.0%), and to help scientific research (54.0%). Conclusions The 3-day atovaquone/proguanil schedule had an impressively high compliance rate, and was well tolerated and accepted by travellers. Further studies are required to assess the effectiveness of this schedule for chemoprophylaxis in travellers.C. L. L. was supported by a fellowship from the Australian National Health and Medical Research Council (grant number 1109035). This study was conducted as part of everyday clinical practice, and participants or their employers paid for the medications

Epidemiologic Findings and Management Response During a Bighorn Sheep Die-Off in the Elkhorn Mountains of West-Central Montana

Bighorn sheep (Ovis canadensis) were introduced into the Elkhorn Mountains of west-central Montana in the mid 1990s. The population increased in number to approximately 250 animals until the winter of 2007-2008 when about 84 percent of the population died from a pneumonia related epizootic. Management actions during the die-off were geared toward removing as many sick animals as possible in efforts to reduce overall mortality. Due to the stage of the epizootic removal of sick sheep was not effective in interrupting the die-off. Samples were collected from bighorn sheep, domestic sheep, mule deer (Odocoileus hemionus), elk (Cervus elaphus) and domestic goats utilizing the same winter range. Pasteurella spp, Moraxella ovis and Mycoplasma ovipneumonia were isolated from lung tissue of dead bighorns and pharyngeal swabs collected from domestic sheep occupying similar range during the epizootic. Both the bighorn sheep and domestic sheep also shared similar gastro-intestinal parasites including Nematodirus spp and Eimeria spp. Testing tissues and fecal samples from sympatric mule deer suggested no shared bacterial pathogens and limited shared gastrointestinal parasites. Evaluation of fecal samples from domestic goats and elk also occupying bighorn sheep range identified few shared parasites that may have contributed to the epizootic

Can the strong get stronger? A laboratory investigation of natural selection for antimicrobial resistance

The students, Sarah Grace Keaveany and Elizabeth Ramsey, completed original research with to investigate 1) standing variation among common bacterial species (Escherichia coli and Stapholococcus epidermidis) in the amount of resistance to triclosan, a common anti-microbial used in hand washes; and 2) the capacity for these bacteria to develop increased resistance to triclosan through selection. The students have developed lab modules based on this research. One module includes a wet lab, where students will culture their own bacteria. The other module allows students to obtain data from photographs of bacterial plates in lieu of a wet lab component

A Self-Lysis Pathway that Enhances the Virulence of a Pathogenic Bacterium

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system

Drug-free holidays: Compliance, tolerability, and acceptability of a 3-day atovaquone/proguanil schedule for pretravel malaria chemoprophylaxis in australian travelers

Background Poor compliance with chemoprophylaxis is a major contributing factor to the risk of malaria in travelers. Pre-travel chemoprophylaxis may improve compliance by enabling “drug-free holidays.” The standard treatment dose of atovaquone/proguanil (250 mg/100 mg, 4 tablets/day for 3 days) provides protection against malaria for at least 4 weeks, and could therefore potentially be used for pre-travel chemoprophylaxis. In this study, we assessed the compliance, tolerability, and acceptability of the 3-day atovaquone/proguanil schedule for malarial chemoprophylaxis. Methods Two hundred thirty-three participants were recruited from 4 specialized travel medicine clinics in Australia. Adults traveling to malaria-endemic areas with low/medium risk for ≤4 weeks were enrolled and prescribed the 3-day schedule of atovaquone/proguanil, completed at least 1 day before departure. Questionnaires were used to collect data on demographics, travel destination, medication compliance, side effects, and reasons for choosing the 3-day schedule. Results Overall, 97.7% of participants complied with the 3-day schedule. Although side effects were reported in 43.3% of the participants, these were well tolerated, and mainly occurred during the first and second days. None of the participants developed malaria. The main reasons for choosing the 3-day schedule over standard chemoprophylaxis options were that it was easier to remember (72.1%), required taking fewer tablets (54.0%), and to help scientific research (54.0%). Conclusions The 3-day atovaquone/proguanil schedule had an impressively high compliance rate, and was well tolerated and accepted by travelers. Further studies are required to assess the effectiveness of this schedule for chemoprophylaxis in travelers.Financial support. C. L. L. was supported by a fellowship from the Australian National Health and Medical Research Council (grant number 1109035). This study was conducted as part of everyday clinical practice, and participants or their employers paid for the medications.Scopu

Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody

<p>Abstract</p> <p>Background</p> <p>Selective neutralization of the IL21/IL21R signaling pathway is a promising approach for the treatment of a variety of autoimmune diseases. Ab-01 is a human neutralizing anti-IL21R antibody. In order to ensure that the activities of Ab-01 are restricted to neutralization even under <it>in vitro </it>cross-linking and <it>in vivo </it>conditions, a comprehensive assessment of agonistic potential of Ab-01 was undertaken.</p> <p>Methods</p> <p><it>In vitro </it>antibody cross-linking and cell culture protocols reported for studies with a human agonistic antibody, TGN1412, were followed for Ab-01. rhIL21, the agonist ligand of the targeted receptor, and cross-linked anti-CD28 were used as positive controls for signal transduction. <it>In vivo </it>agonistic potential of Ab-01 was assessed by measuring expression levels of cytokine storm-associated and IL21 pathway genes in blood of cynomolgus monkeys before and after IV administration of Ab-01.</p> <p>Results</p> <p>Using a comprehensive set of assays that detected multiple activation signals in the presence of the positive control agonists, <it>in vitro </it>Ab-01-dependent activation was not detected in either PBMCs or the rhIL21-responsive cell line Daudi. Furthermore, no difference in gene expression levels was detected in blood before and after <it>in vivo </it>Ab-01 dosing of cynomolgus monkeys.</p> <p>Conclusions</p> <p>Despite efforts to intentionally force an agonistic signal from Ab-01, none could be detected.</p

Exercise counselling and referral in cancer care: An international scoping survey of health care practitioners’ knowledge, practices, barriers, and facilitators

Purpose: Evidence supports the role of prescribed exercise for cancer survivors, yet few are advised to exercise by a healthcare practitioner (HCP). We sought to investigate the gap between HCPs’ knowledge and practice from an international perspective. Methods: An online questionnaire was administered to HCPs working in cancer care between February 2020 and February 2021. The questionnaire assessed knowledge, beliefs, and practices regarding exercise counselling and referral of cancer survivors to exercise programs. Results: The questionnaire was completed by 375 participants classified as medical practitioners (42 %), nurses (28 %), exercise specialists (14 %), and non-exercise allied health practitioners (16 %). Between 35 and 50 % of participants self-reported poor knowledge of when, how, and which cancer survivors to refer to exercise programs or professionals, and how to counsel based on exercise guidelines. Commonly reported barriers to exercise counselling were safety concerns, time constraints, cancer survivors being told to rest by friends and family, and not knowing how to screen people for suitability to exercise (40 – 48 %). Multivariable logistic regression models including age, gender, practitioner group, leisure-time physical activity, and recall of guidelines found significant effects for providing specific exercise advice (χ2(7) = 117.31, p \u3c .001), discussing the role of exercise in symptom management (χ2(7) = 65.13, p \u3c .001) and cancer outcomes (χ2(7) = 58.69, p \u3c .001), and referring cancer survivors to an exercise program or specialist (χ2(7) = 72.76, p \u3c .001). Conclusion: Additional education and practical support are needed to equip HCPs to provide cancer survivors with exercise guidelines, resources, and referrals to exercise specialists

Examining the Interface Between Substance Misuse and Intimate Partner Violence

There is considerable theoretical and empirical support for a link between substance misuse and perpetration and victimization of intimate partner violence. This review briefly summarizes this literature and highlights current research that addresses the interface between treatment for substance abuse and intimate partner violence. Suggestions for future research and clinical implications are provided

Feasibility and safety of a 6-month exercise program to increase bone and muscle strength in children with juvenile idiopathic arthritis

Background: Arthritis in childhood can be associated with muscle weakness around affected joints, low bone mass and low bone strength. Exercise is recognized as an important part of management of children with juvenile idiopathic arthritis (JIA) but the exercise prescription to best promote bone and muscle health is unknown. We therefore aimed to: 1. assess feasibility and safety of a 6-month home- and group-based exercise program for children with JIA; 2. estimate the effect of program participation on bone mass and strength, muscle function and clinical outcomes and 3. determine if any positive changes in bone and muscle outcomes are maintained 6 months later. Methods: We recruited 24 children with JIA who were part of the Linking Exercise, Physical Activity and Pathophysiology in Childhood Arthritis (LEAP) study to participate in a 6-month home-based exercise program involving jumping and handgrip exercises, resistance training and one group exercise session per month. We assessed lumbar spine bone mass (dual energy X-ray absorptiometry), distal tibia and radius bone microarchitecture and strength (high-resolution peripheral quantitative computed tomography), muscle function (jumping mechanography, dynamometry) and clinical outcomes (joint assessment, function, health-related quality of life) at baseline, 6- and 12-months. Adherence was assessed using weekly activity logs. Results: Thirteen children completed the 6-month intervention. Participants reported 9 adverse events and post-exercise pain was rare (0.4%). Fatigue improved, but there were no other sustained improvements in muscle, bone or clinical outcomes. Adherence to the exercise program was low (47%) and decreased over time. Conclusion: Children with JIA safely participated in a home-based exercise program designed to enhance muscle and bone strength. Fatigue improved, which may in turn facilitate physical activity participation. Prescribed exercise posed adherence challenges and efforts are needed to address facilitators and barriers to participation in and adherence to exercise programs among children with JIA. Trial registration: Data of the children with JIA are from the LEAP study (Canadian Institutes of Health Research (CIHR; GRANT# 107535). http://www.leapjia.com/