Drug therapy for symptoms associated with anxiety in adult palliative care patients

Background: This is an update of a Cochrane Review first published in 2004 (Issue 1) and previously updated in 2012 (Issue 10). Anxiety is common in palliative care patients. It can be a natural response to the complex uncertainty of having a life-limiting illness or impending death, but it may represent a clinically significant issue in its own right. Objectives: To assess the effectiveness of drug therapy for treating symptoms of anxiety in adults with a progressive life-limiting illness who are thought to be in their last year of life. Search methods: We ran the searches for this update to May 2016. We searched the CENTRAL, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), PsychLIT (Silver Platter) and PsycINFO (Ovid). We searched seven trials registers and seven pharmaceutical industry trials registers. We handsearched the conference abstracts of the European Association of Palliative Care. Selection criteria: Randomised controlled trials which examined the effect of drug therapy for the treatment of symptoms of anxiety in adult palliative care patients, that is, people with a known progressive life-limiting illness that is no longer responsive to curative treatment, including advanced heart, respiratory and neurological diseases (including dementia). Comparator treatments included placebo; another drug therapy or different dose schedule; or a non-drug intervention such as counselling, cognitive behaviour therapies or relaxation therapies. Data collection and analysis: Two review authors independently screened titles and abstracts to identify potentially relevant papers for inclusion in the review. We sought full-text reports for all papers retained at this stage and two reviews authors independently assessed these for inclusion in the review. We planned to assess risk of bias and extract data including information on adverse events. We planned to assess the evidence using GRADE and to create a 'Summary of findings' table. Main results: In this update, we identified 707 potentially relevant papers and of these we sought the full-text reports of 10 papers. On examination of these full-text reports, we excluded eight and two are awaiting classification as we have insufficient information to make a decision. Thus, in this update, we found no studies which met our inclusion criteria. For the original review, we identified, and then excluded, the full-text reports of six potentially relevant studies. For the 2012 update, we sought, and excluded, two full-text reports. Thus, we found no studies that assessed the effectiveness of drugs to treat symptoms of anxiety in palliative care patients. Authors' conclusions: There is a lack of evidence to draw a conclusion about the effectiveness of drug therapy for symptoms of anxiety in adult palliative care patients. To date, we have found no studies that meet the inclusion criteria for this review. We are awaiting further information for two studies which may be included in a future update. Randomised controlled trials which assess management of anxiety as a primary endpoint are required to establish the benefits and harms of drug therapy for the treatment of anxiety in palliative care

National survey of the injury prevention activities of children's centres

Children's centres were established across England to provide a range of services including early education, social care and health to pre-school children and their families. We surveyed children's centres to ascertain the activities they were undertaking to prevent unintentional injuries in the under fives. A postal questionnaire was sent to a sample of children's centre managers (n = 694). It included questions on current activities, knowledge and attitudes to injury prevention, health priorities and partnership working. Responses were received from 384 (56%) children's centres. Overall, 58% considered unintentional injury prevention to be one of the three main child health priorities for their centre. Over half the respondents (59%) did not know if there was an injury prevention group in their area, and 21% did not know if there was a home safety equipment scheme. Knowledge of how child injury deaths occur in the home was poor. Only 11% knew the major cause of injury deaths in children under five. Lack of both staff time and funding were seen as important barriers by children's centre staff to undertake injury prevention activities. Nearly all stated that training (97%) and assistance with planning injury prevention (94%) would be helpful to their centres. Children's centres need further support if they are to effectively tackle this important public health area

Cycling infrastructure for reducing cycling injuries in cyclists

Background: Cycling is an attractive form of transport. It is beneficial to the individual as a form of physical activity that may fit more readily into an individual’s daily routine, such as for cycling to work and to the shops, than other physical activities such as visiting a gym. Cycling is also beneficial to the wider community and the environment as a result of fewer motorised journeys. Cyclists are seen as vulnerable road users who are frequently in close proximity to larger and faster motorised vehicles. Cycling infrastructure aims to make cycling both more convenient and safer for cyclists. This review is needed to guide transport planning. Objectives: To: 1. evaluate the effects of different types of cycling infrastructure on reducing cycling injuries in cyclists, by type of infrastructure; 2. evaluate the effects of cycling infrastructure on reducing the severity of cycling injuries in cyclists; 3. evaluate the effects of cycling infrastructure on reducing cycling injuries in cyclists with respect to age, sex and social group. Search methods: We ran the most recent search on 2nd March 2015. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), Embase Classic + Embase(OvidSP), PubMed and 10 other databases. We searched websites, handsearched conference proceedings, screened reference lists of included studies and previously published reviews and contacted relevant organisations. Selection criteria: We included randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted time series studies which evaluated the effect of cycling infrastructure (such as cycle lanes, tracks or paths, speed management, roundabout design) on cyclist injury or collision rates. Studies had to include a comparator, that is, either no infrastructure or a different type of infrastructure. We excluded studies that assessed collisions that occurred as a result of competitive cycling. Data collection and analysis: Two review authors examined the titles and abstracts of papers obtained from searches to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. We carried out a meta-analysis using the random-effects model where at least three studies reported the same intervention and outcome. Where there were sufficient studies, as a secondary analysis we accounted for changes in cyclist exposure in the calculation of the rate ratios. We rated the quality of the evidence as ‘high’, ‘moderate’,‘low’ or ‘very low’ according to the GRADE approach for the installation of cycle routes and networks. Main results: We identified 21 studies for inclusion in the review: 20 controlled before-after (CBA) studies and one interrupted time series (ITS) study. These evaluated a range of infrastructure including cycle lanes, advanced stop lines, use of colour, cycle tracks, cycle paths, management of the road network, speed management, cycle routes and networks, roundabout design and packages of measures. No studies reported medically-attended or self-reported injuries. There was no evidence that cycle lanes reduce the rate of cycle collisions (rate ratio 1.21, 95% CI 0.70 to 2.08). Taking into account cycle flow, there was no difference in collisions for cyclists using cycle routes and networks compared with cyclists not using cycle routes and networks (RR 0.40, 95% CI 0.15 to 1.05). There was statistically significant heterogeneity between the studies (I² = 75%, Chi² = 8.00 df = 2, P = 0.02) for the analysis adjusted for cycle flow. We judged the quality of the evidence regarding cycle routes and networks as very low and we are very uncertain about the estimate. These analyses are based on findings from CBA studies. From data presented narratively, the use of 20 mph speed restrictions in urban areas may be effective at reducing cyclist collisions. Redesigning specific parts of cycle routes that may be particularly busy or complex in terms of traffic movement may be beneficial to cyclists in terms of reducing the risk of collision. Generally, the conversion of intersections to roundabouts may increase the number of cycle collisions. In particular, the conversion of intersections to roundabouts with cycle lanes marked as part of the circulating carriageway increased cycle collisions. However, the conversion of intersections with and without signals to roundabouts with cycle paths may reduce the odds of collision. Both continuing a cycle lane across the mouth of a side road with a give way line onto the main road, and cycle tracks, may increase the risk of injury collisions in cyclists. However, these conclusions are uncertain, being based on a narrative review of findings from included studies. There is a lack of evidence that cycle paths or advanced stop lines either reduce or increase injury collisions in cyclists. There is also insufficient evidence to draw any robust conclusions concerning the effect of cycling infrastructure on cycling collisions in terms of severity of injury, sex, age, and level of social deprivation of the casualty. In terms of quality of the evidence, there was little matching of intervention and control sites. In many studies, the comparability of the control area to the intervention site was unclear and few studies provided information on other cycling infrastructures that may be in place in the control and intervention areas. The majority of studies analysed data routinely collected by organisations external to the study team, thus reducing the risk of bias in terms of systematic differences in assessing outcomes between the control and intervention groups. Some authors did not take regression-to-mean effects into account when examining changes in collisions. Longer data collection periods pre- and post-installation would allow for regression-to-mean effects and also seasonal and time trends in traffic volume to be observed. Few studies adjusted cycle collision rates for exposure. Authors’ conclusions: Generally, there is a lack of high quality evidence to be able to draw firm conclusions as to the effect of cycling infrastructure on cycling collisions. There is a lack of rigorous evaluation of cycling infrastructure

School-based education programmes for the prevention of unintentional injuries in children and young people.

Background: Unintentional injuries are the leading cause of death in children aged four to 18 years and are a major cause of ill health. The school setting offers the opportunity to deliver preventive interventions to a large number of children and has been used to address a range of public health problems. However, the effectiveness of the school setting for the prevention of different injury mechanisms in school-aged children is not well understood. Objectives: To assess the effects of school-based educational programmes for the prevention of injuries in children and evaluate their impact on improving children's safety skills, behaviour and practices, and knowledge, and assess their cost-effectiveness. Search methods: We ran the most recent searches up to 16 September 2016 for the following electronic databases: Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials; Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R); Embase and Embase Classic (Ovid); ISI Web of Science: Science Citation Index Expanded; ISI Web of Science Conference Proceedings Citation Index-Science; ISI Web of Science: Social Sciences Citation Index; ISI Web of Science: Conference Proceedings Citation Index - Social Sciences & Humanities; and the 14 October 2016 for the following electronic databases: Health Economics Evaluations Database (HEED); Health Technology Assessment Database (HTA); CINAHL Plus (EBSCO); ZETOC; LILACS; PsycINFO; ERIC; Dissertation Abstracts Online; IBSS; BEI; ASSIA; CSA Sociological Abstracts; Injury Prevention Web; SafetyLit; EconLit (US); PAIS; UK Clinical Research Network Study Portfolio; Open Grey; Index to Theses in the UK and Ireland; Bibliomap and TRoPHI. Selection criteria: We included randomised controlled trials (RCTs), non-randomised controlled trials (non-RCTs), and controlled before-and-after (CBA) studies that evaluated school-based educational programmes aimed at preventing a range of injury mechanisms. The primary outcome was self-reported or medically attended unintentional (or unspecified intent) injuries and secondary outcomes were observed safety skills, observed behaviour, self-reported behaviour and safety practices, safety knowledge, and health economic outcomes. The control groups received no intervention, a delayed injury-prevention intervention or alternative school-based curricular activities. We included studies that aimed interventions at primary or secondary prevention of injuries from more than one injury mechanism and were delivered, in part or in full, in schools catering for children aged four to 18 years. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two review authors identified relevant trials from title and abstracts of studies identified in searches and two review authors extracted data from the included studies and assessed risk of bias. We grouped different types of interventions according to the outcome assessed and the injury mechanism targeted. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies. Main results: The review included 27 studies reported in 30 articles. The studies had 73,557 participants with 12 studies from the US; four from China; two from each of Australia, Canada, the Netherlands and the UK; and one from each of Israel, Greece and Brazil. Thirteen studies were RCTs, six were non-RCTs and eight were CBAs. Of the included studies, 18 provided some element of the intervention in children aged four to 11 years, 17 studies included children aged 11 to 14 years and nine studies included children aged 14 to 18 years. The overall quality of the results was poor, with the all studies assessed as being at high or unclear risks of bias across multiple domains, and varied interventions and data collection methods employed. Interventions comprised information-giving, peer education or were multi-component. Seven studies reported the primary outcome of injury occurrence and only three of these were similar enough to combine in a meta-analysis, with a pooled incidence rate ratio of 0.73 (95% confidence interval (CI) 0.49 to 1.08; 2073 children) and substantial statistical heterogeneity (I2 = 63%). However, this body of evidence was low certainty, due to concerns over this heterogeneity (inconsistency) and imprecision. This heterogeneity may be explained by the non-RCT study design of one of the studies, as a sensitivity analysis with this study removed found stronger evidence of an effect and no heterogeneity (I2 = 0%). Two studies report an improvement in safety skills in the intervention group. Likewise, the four studies measuring observed safety behaviour reported an improvement in the intervention group relative to the control. Thirteen out of 19 studies describing self-reported behaviour and safety practices showed improvements, and of the 21 studies assessing changes in safety knowledge, 19 reported an improvement in at least one question domain in the intervention compared to the control group. However, we were unable to pool data for our secondary outcomes, so our conclusions were limited, as they were drawn from highly diverse single studies and the body of evidence was low (safety skills) or very low (behaviour, safety knowledge) certainty. Only one study reported intervention costs but did not undertake a full economic evaluation (very low certainty evidence). Authors' conclusions: There is insufficient evidence to determine whether school-based educational programmes can prevent unintentional injuries. More high-quality studies are needed to evaluate the impact of educational programmes on injury occurrence. There is some weak evidence that such programmes improve safety skills, behaviour/practices and knowledge, although the evidence was of low or very low quality certainty. We found insufficient economic studies to assess cost-effectiveness

GLP-1 receptor agonists for Parkinson's disease (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson’s disease. We will differentiate, as far as possible between neuroprotective and symptomatic effects

Adenoidectomy for otitis media with effusion (OME) in children

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition. OBJECTIVES: To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared adenoidectomy (alone, or in combination with ventilation tubes) with either no treatment or non-surgical treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes (determined following a multi-stakeholder prioritisation exercise): 1) hearing, 2) otitis media-specific quality of life, 3) haemorrhage. SECONDARY OUTCOMES: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function, 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 10 studies (1785 children). Many of the studies used concomitant interventions for all participants, including insertion of ventilation tubes or myringotomy. All included studies had at least some concerns regarding the risk of bias. We report results for our main outcome measures at the longest available follow-up. We did not identify any data on disease-specific quality of life for any of the comparisons. Further details of additional outcomes and time points are reported in the review. 1) Adenoidectomy (with or without myringotomy) versus no treatment/watchful waiting (three studies) After 12 months there was little difference in the proportion of children whose hearing had returned to normal, but the evidence was very uncertain (adenoidectomy 68%, no treatment 70%; risk ratio (RR) 0.97, 95% confidence interval (CI) 0.65 to 1.46; number needed to treat to benefit (NNTB) 50; 1 study, 42 participants). There is a risk of haemorrhage from adenoidectomy, but the absolute risk appears small (1/251 receiving adenoidectomy compared to 0/229, Peto odds ratio (OR) 6.77, 95% CI 0.13 to 342.54; 1 study, 480 participants; moderate certainty evidence). The risk of persistent OME may be slightly lower after two years in those receiving adenoidectomy (65% versus 73%), but again the difference was small (RR 0.90, 95% CI 0.81 to 1.00; NNTB 13; 3 studies, 354 participants; very low-certainty evidence). 2) Adenoidectomy (with or without myringotomy) versus non-surgical treatment No studies were identified for this comparison. 3) Adenoidectomy and bilateral ventilation tubes versus bilateral ventilation tubes (four studies) There was a slight increase in the proportion of ears with a return to normal hearing after six to nine months (57% adenoidectomy versus 42% without, RR 1.36, 95% CI 0.98 to 1.89; NNTB 7; 1 study, 127 participants (213 ears); very low-certainty evidence). Adenoidectomy may give an increased risk of haemorrhage, but the absolute risk appears small, and the evidence was uncertain (2/416 with adenoidectomy compared to 0/375 in the control group, Peto OR 6.68, 95% CI 0.42 to 107.18; 2 studies, 791 participants). The risk of persistent OME was similar for both groups (82% adenoidectomy and ventilation tubes compared to 85% ventilation tubes alone, RR 0.96, 95% CI 0.86 to 1.07; very low-certainty evidence). 4) Adenoidectomy and unilateral ventilation tube versus unilateral ventilation tube (two studies) Slightly more children returned to normal hearing after adenoidectomy, but the confidence intervals were wide (57% versus 46%, RR 1.24, 95% CI 0.79 to 1.96; NNTB 9; 1 study, 72 participants; very low-certainty evidence). Fewer children may have persistent OME after 12 months, but again the confidence intervals were wide (27.2% compared to 40.5%, RR 0.67, 95% CI 0.35 to 1.29; NNTB 8; 1 study, 74 participants). We did not identify any data on haemorrhage. 5) Adenoidectomy and ventilation tubes versus no treatment/watchful waiting (two studies) We did not identify data on the proportion of children who returned to normal hearing. However, after two years, the mean difference in hearing threshold for those allocated to adenoidectomy was -3.40 dB (95% CI -5.54 to -1.26; 1 study, 211 participants; very low-certainty evidence). There may be a small reduction in the proportion of children with persistent OME after two years, but the evidence was very uncertain (82% compared to 90%, RR 0.91, 95% CI 0.82 to 1.01; NNTB 13; 1 study, 232 participants). We noted that many children in the watchful waiting group had also received surgery by this time point. 6) Adenoidectomy and ventilation tubes versus non-surgical treatment No studies were identified for this comparison. AUTHORS' CONCLUSIONS: When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children

Metformin for endometrial hyperplasia (Review)

Background Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. Objectives To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. Search methods We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar,OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015. Selection criteria We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. Data collection and analysis Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment. Main results We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision. We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59)provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others. Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37,one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. Authors’ conclusions At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question

The feasibility of using a parenting programme for the prevention of unintentional home injuries in the under-fives: A cluster randomised controlled trial

Background: Unintentional injury is the leading cause of preventable death of children over the age of 1 year in the UK and a major cause of attendance at emergency departments. Children having one injury are at increased risk of further injuries. Parenting programmes can reduce injuries in preschool children if delivered in the home and on a one-to-one basis. It is not known if group-based programmes delivered outside the home are effective. Objectives: To develop (1) a parenting programme to prevent recurrent unintentional home injuries in preschool children and (2) a tool for parents to report unintentional home injuries occurring to their preschool children. To assess the feasibility of delivering and evaluating the parenting programme through a cluster randomised controlled trial, specifically to (1) assess methods for the recruitment and retention of parents; (2) determine the training, equipment and facilities needed for the delivery of the programme; (3) establish appropriate primary and secondary outcome measures and methods for their collection; (4) determine how 'normal care' in a comparison arm should be defined; and (5) determine the resource utilisation and costing data that would need to be collected for the cost-effectiveness component of a future trial; and (6) produce estimates of effect sizes to inform sample size estimation for a main trial. Design: Feasibility multicentre, cluster, randomised, unblinded trial. Setting: Eight children's centres in Bristol and Nottingham, UK. Participants: Ninety-six parents of preschool children who had sustained an unintentional injury requiring medical attention in the previous 12 months. Interventions: The First-aid Advice and Safety Training (FAST) parent programme, comprising parenting support and skills combined with first aid and home safety advice. Main outcome measures: Parent-reported medically attended injuries in the index child and any preschool siblings sustained during a 6-month period of observation. Results: An 8-week parenting programme was produced, designed with participant-friendly, incrementally progressive content. A slimline, month-to-a-view injury calendar, spiral bound and suitable for hanging on a wall, was designed for parents to record injuries occurring to their preschool children during the 6-month period of observed time. Fifty-one parents were recruited (40 meeting eligibility criteria plus 11 following 'open invite' to participate); 15 parents completed the FAST parent programme and 49 provided data at baseline and during follow-up. Completion of the programme was significantly greater for participants using the 'open invite' approach (85%) than for those recruited using the original eligibility criteria (31%). Prototype resource use checklists, unit costs and total costs were developed for phases 0, 1 and 2 of the study for use in a future trial. Conclusions: This feasibility study has developed an innovative injury prevention intervention and a tool to record parent-reported injuries in preschool children. It was not feasible to recruit parents of children who had sustained a recent injury, or to ask health visitor teams to identify potential participants and to deliver the programme. A trial should target all families attending children's centres in disadvantaged areas. The intervention could be delivered by a health professional supported by a member of the children's centre team in a community setting. Trial registration: Current Controlled Trials ISRCTN03605270. Source of funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 3. See the NIHR Journals Library website for further project information. © Queen's Printer and Controller of HMSO 2014

GLP-1 receptor agonists for Parkinson's disease (Review)

Background Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed fortreatment oftype 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic eEicacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD. Objectives To evaluate the eEectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. Search methods We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020. Selection criteria We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment. Data collection and analysis Two reviewauthors independently assessed studies forinclusion, extracted data, and assessed risk of bias.We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author. Main results Through our searches, we retrieved 99 unique records, of which two met ourinclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the oE-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The diEerence in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no eEect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no eEect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8). Authors' conclusions Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persistfor some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying eEect. SAEs were unlikely to be related to treatment. The eEectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists

Subsoil contraints and their management: Overview from five years of R&D

Subsoil constraints cost the grains industry more than $1.6b in lost production each year. Diagnosing and mapping subsoil constraints (SSC) was achieved at a shire scale using the DPIRD soils database and historic surveys