Precipitation modification by ionization

Rainfall is hypothesised to be influenced by droplet charge, which is related to the global circuit current flowing through clouds. This is tested through examining a major global circuit current increase following release of artificial radioactivity. Significant changes occurred in daily rainfall distribution in the Shetland Islands, away from pollution. Daily rainfall changed by 24%, and local cloud optically thickened, within the nuclear weapons test period. This supports expectations of electrically induced microphysical changes in liquid water clouds from additional ionisation

A multifactorial intervention for frail older people is more than twice as effective among those who are compliant: complier average causal effect analysis of a randomised trial

AbstractQuestion: What is the effect of a multifactorial intervention on frailty and mobility in frail older people who comply with their allocated treatment? Design: Secondary analysis of a randomised, controlled trial to derive an estimate of complier average causal effect (CACE) of treatment. Participants: A total of 241 frail community-dwelling people aged ≥ 70 years. Intervention: Intervention participants received a 12-month multidisciplinary intervention targeting frailty, with home exercise as an important component. Control participants received usual care. Outcome measures: Primary outcomes were frailty, assessed using the Cardiovascular Health Study criteria (range 0 to 5 criteria), and mobility measured using the 12-point Short Physical Performance Battery. Outcomes were assessed 12 months after randomisation. The treating physiotherapist evaluated the amount of treatment received on a 5-point scale. Results: 216 participants (90%) completed the study. The median amount of treatment received was 25 to 50% (range 0 to 100). The CACE (ie, the effect of treatment in participants compliant with allocation) was to reduce frailty by 1.0 frailty criterion (95% CI 0.4 to 1.5) and increase mobility by 3.2 points (95% CI 1.8 to 4.6) at 12 months. The mean CACE was substantially larger than the intention-to-treat effect, which was to reduce frailty by 0.4 frailty criteria (95% CI 0.1 to 0.7) and increase mobility by 1.4 points (95% CI 0.8 to 2.1) at 12 months. Conclusion: Overall, compliance was low in this group of frail people. The effect of the treatment on participants who comply with allocated treatment was substantially greater than the effect of allocation on all trial participants. Trial registration: Australian and New Zealand Trial Registry ANZCTRN12608000250336. [Fairhall N, Sherrington C, Cameron ID, Kurrle SE, Lord SR, Lockwood K, Herbert RD (2016) A multifactorial intervention for frail older people is more than twice as effective among those who are compliant: complier average causal effect analysis of a randomised trial. Journal of Physiotherapy 63: 40–44

Effectiveness of Oral Nutritional Supplementation for Older Women after a Fracture: Rationale, Design and Study of the Feasibility of a Randomized Controlled Study

<p>Abstract</p> <p>Background</p> <p>Malnutrition is a problem for many older people recovering from a hip and other major fractures. Oral supplementation with high calorie high protein nutrients is a simple intervention that may help older people with fractures to improve their recovery in terms of rehabilitation time, length of hospital stay and mortality. This paper reports a pilot study to test the feasibility of a trial initiated in a hospital setting with an oral supplement to older people with recent fractures.</p> <p>Method</p> <p>A randomized controlled trial with 44 undernourished participants admitted to a hospital following a fracture. The intervention group (n = 23) received a high calorie high protein supplement for forty days in addition to their diet of choice. The control group (n = 21) received high protein milk during their hospital stay in addition to their diet of choice and their usual diet when discharged from hospital.</p> <p>Results</p> <p>All participants were women and their mean age was 85.3 (± 6.1) years. Twenty nine (65%) participants had a hip fracture. At baseline no differences were measured between the two groups regarding their nutritional status, their cognitive ability or their abilities in activities of daily living. There were no significant differences between the intervention and control group with reference to nutritional or functional parameters at 40 day and 4 month follow-ups. Median length of stay in hospital was 18.0 days, with 12 participants being readmitted for a median of 7.0 days.</p> <p>Conclusion</p> <p>It is feasible to perform a randomised trial in a hospital and community setting to test the effect of an oral high energy high protein supplement for older people. Due to the limited number of participants and incomplete adherence with use of the supplements no conclusion can be drawn about the efficacy or effectiveness of this intervention.</p

Treating frailty-a practical guide

Frailty is a common syndrome that is associated with vulnerability to poor health outcomes. Frail older people have increased risk of morbidity, institutionalization and death, resulting in burden to individuals, their families, health care services and society. Assessment and treatment of the frail individual provide many challenges to clinicians working with older people. Despite frailty being increasingly recognized in the literature, there is a paucity of direct evidence to guide interventions to reduce frailty. In this paper we review methods for identification of frailty in the clinical setting, propose a model for assessment of the frail older person and summarize the current best evidence for treating the frail older person. We provide an evidence-based framework that can be used to guide the diagnosis, assessment and treatment of frail older people

Frailty Intervention Trial (FIT)

<p>Abstract</p> <p>Background</p> <p>Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity). Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty.</p> <p>We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people.</p> <p>Methods and Design</p> <p>A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period.</p> <p>Discussion</p> <p>This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation. The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trails Registry: ACTRN12608000250336.</p

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society