Oral dosing with papaya latex is an effective anthelmintic treatment for sheep infected with Haemonchus contortus

Background The cysteine proteinases in papaya latex have been shown to have potent anthelmintic properties in monogastric hosts such as rodents, pigs and humans, but this has not been demonstrated in ruminants. Methods In two experiments, sheep were infected concurrently with 5,000 infective larvae of Haemonchus contortus and 10,000 infective larvae of Trichostrongylus colubriformis and were then treated with the supernatant from a suspension of papaya latex from day 28 to day 32 post-infection. Faecal egg counts were monitored from a week before treatment until the end of the experiment and worm burdens were assessed on day 35 post-infection. Results We found that the soluble fraction of papaya latex had a potent in vivo effect on the abomasal nematode H. contortus, but not on the small intestinal nematode T. colubriformis. This effect was dose-dependent and at tolerated levels of gavage with papaya latex (117 μmol of active papaya latex supernatant for 4 days), the H. contortus worm burdens were reduced by 98%. Repeated treatment, daily for 4 days, was more effective than a single dose, but efficacy was not enhanced by concurrent treatment with the antacid cimetidine. Conclusions Our results provide support for the idea that cysteine proteinases derived from papaya latex may be developed into novel anthelmintics for the treatment of lumenal stages of gastro-intestinal nematode infections in sheep, particularly those parasitizing the abomasum

Adaptation and implementation of a mobile phone–based remote symptom monitoring system for people with cancer in Europe

Background: There has been an international shift in health care, which has seen an increasing focus and development of technological and personalized at-home interventions that aim to improve health outcomes and patient-clinician communication. However, there is a notable lack of empirical evidence describing the preparatory steps of adapting and implementing technology of this kind across multiple countries and clinical settings. Objective: This study aimed to describe the steps undertaken in the preparation of a multinational, multicenter randomized controlled trial (RCT) to test a mobile phone–based remote symptom monitoring system, that is, Advanced Symptom Management System (ASyMS), designed to enhance management of chemotherapy toxicities among people with cancer receiving adjuvant chemotherapy versus standard cancer center care. Methods: There were 13 cancer centers across 5 European countries (Austria, Greece, Ireland, Norway, and the United Kingdom). Multiple steps were undertaken, including a scoping review of empirical literature and clinical guidelines, translation and linguistic validation of study materials, development of standardized international care procedures, and the integration and evaluation of the technology within each cancer center. Results: The ASyMS was successfully implemented and deployed in clinical practices across 5 European countries. The rigorous and simultaneous steps undertaken by the research team highlighted the strengths of the system in clinical practice, as well as the clinical and technical changes required to meet the diverse needs of its intended users within each country, before the commencement of the RCT. Conclusions: Adapting and implementing this multinational, multicenter system required close attention to diverse considerations and unique challenges primarily related to communication and clinical and technical issues. Success was dependent on collaborative and transparent communication among academics, the technology industry, translation partners, patients, and clinicians as well as a simultaneous and rigorous methodological approach within the 5 relevant countries

Leucine and perindopril to improve physical performance in people over 70 years with sarcopenia : the LACE factorial RCT

Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 8. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease:the BiCARB RCT

Acknowledgements: We would like to acknowledge the support received from the NHS Scotland Support for Science scheme and the NIHR Renal and Ageing Comprehensive Research Networks; the work of all the investigators, research nurses and study teams at the different sites and the Tayside CTU staff; and, most importantly, all those with kidney disease who participated in the trial. In addition, we acknowledge the support and advice that we received from the independent TSC members (Professor David Stott, Professor Patrick Mark, Professor Tahir Masud and Mr Alex Stephen) and the independent DMC members (Professor Alex McConnachie, Professor David Wheeler, Dr Nicosha de Souza and Dr Andrew Clegg). Professor Marion McMurdo and Dr Simon Ogston were co-applicants on the original proposal, but demitted from the project on retirement and were not involved in the creation of this report. Trial registration: Current Controlled Trials ISRCTN09486651 and EudraCT 2011-005271-16. The systematic review is registered as PROSPERO CRD42018112908. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 27. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Recruitment strategies for sarcopenia trials – lessons from the LACE randomised controlled trial

Background: Sarcopenia is rarely diagnosed and is not recorded electronically in routine clinical care, posing challenges to trial recruitment. We describe the performance of four components of a strategy to efficiently recruit participants with sarcopenia to a trial of perindopril and/or leucine for sarcopenia: primary care vs. hospital recruitment, a comparison of central vs. local telephone pre-screening, performance of a questionnaire on physical function conducted as part of the pre-screening telephone call, and performance of bioimpedance measurement to identify low muscle mass. Methods: Hospital-based recruitment took place through inpatient and outpatient geriatric medicine services. Local research nurses reviewed medical notes and approached potentially eligible patients. Primary care recruitment reviewed primary care lists from collaborating practices, sending mailshots to patients aged 70 and over who were not taking angiotensin-converting enzyme inhibitors. Telephone pre-screening was conducted either by research nurses at each site or centrally by Tayside Clinical Trials Unit. The 10-point SARC-F questionnaire was used for pre-screening. De-identified recruitment information was held on a central electronic tracking system and analysed using SPSS. Bioimpedance was measured using the Akern BIA 101 system, with the Sergi equation used to estimate lean mass. Results: Fourteen UK sites recruited to the trial. The 1202 sets of notes in hospital-based care were reviewed at these sites; 7 participants (0.6% of total notes screened) were randomized. From primary care, 13 808 invitations were sent; 138 (1.0% of total invited) were randomized. 633/2987 primary care respondents were pre-screened centrally; the mean number of calls per respondent was 2.3. For 10 sites where central and local pre-screening could be compared, the conversion rate from pre-screening to randomization was 18/588 (3.1%) for centralized calls, compared with 73/1814 (4.0%) for local pre-screening calls (P = 0.29). A weak relationship was seen between higher (worse) SARC-F score at screening and lower likelihood of progression to randomization (r = −0.08, P = 0.03). Muscle mass estimates generated using the Sergi equation were systematically biased, and a recalibrated equation for bioimpedance-estimated muscle mass was derived. Conclusions: Primary care recruitment led to higher response rates and overall numbers randomized than hospital-based recruitment. Centralized pre-screening saved local research nurses' time but did not improve conversion to randomization. SARC-F did not help to target screening activity in this sarcopenia trial, and a recalibration of the equation for estimating muscle mass from bioimpedance measures may improve accuracy of the screening process

The eSMART study protocol : a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer

Introduction While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients. Methods and analysis A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes). Ethics and dissemination Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts. Trial registration number NCT02356081

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.</p

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia.Methods: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) =0.26 and rs2854464, MAF =0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial.Results: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p=0.023) and had higher arm fat mass, (median higher by 15%, p=0.008), and leg fat mass (median higher by 14%, p=0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj=0.024). No associations (adjusted or unadjusted) were seen in females.Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p=0.017) and greater arm fat mass (median higher by 16%, p=0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone.Conclusion: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals

Adaptation and implementation of a multinational eHealth intervention for people with cancer : reflections from the field

Background: There has been an international shift in healthcare which has seen an increasing focus and development of technological and personalized at-home interventions which aim to improve health outcomes and patient-clinician communication. However, there is a notable lack of empirical evidence describing the preparatory steps of adapting and implementing technology of this kind across multiple countries and clinical settings. Objective: To describe the steps undertaken in the preparation of a multinational, multicentre randomized controlled trial to test a mobile phone-based remote symptom monitoring system, i.e. Advanced Symptom Management System Remote Technology (ASyMS), designed to enhance management of chemotherapy toxicities amongst people with cancer receiving adjuvant chemotherapy versus standard cancer centre care. Methods: Multiple steps were undertaken, including; a scoping review of empirical literature and clinical guidelines, translation and linguistic validation of study materials, development of standardised international care procedures and the integration and evaluation of the technology within each cancer centre. Results: ASyMS was successfully implemented and deployed in clinical practice across five European countries. The rigorous and simultaneous steps undertaken by the research team highlighted the strengths of the system in clinical practice, as well as the clinical and technical changes required to meet the diverse needs of its intended users within each country, prior to the commencement of the randomized controlled trial. Conclusions: Adapting and implementing this multinational, multicentre system required close attention to diverse considerations and unique challenges, primarily related to communication, clinical and technical issues. Success was dependent on collaborative and transparent communication amongst academics, technology industry, translation partners, patients, and clinicians as well as a simultaneous and rigorous methodological approach within the five relevant countries