A Mock Randomized Controlled Trial With Audience Response Technology for Teaching and Learning Epidemiology.

The study's objective was to apply and assess an active learning approach to epidemiology and critical appraisal. Active learning comprised a mock, randomized controlled trial (RCT) conducted with learners in 3 countries. The mock trial consisted of blindly eating red Smarties candy (intervention) compared to yellow Smarties (control) to determine whether red Smarties increase happiness. Audience response devices were employed with the 3-fold purposes to produce outcome data for analysis of the effects of red Smarties, identify baseline and subsequent changes in participant's knowledge and confidence in understanding of RCTs, and assess the teaching approach. Of those attending, 82% (117 of 143 learners) participated in the trial component. Participating in the mock trial was a positive experience, and the use of the technology aided learning. The trial produced data that learners analyzed in "real time" during the class. The mock RCT is a fun and engaging approach to teaching RCTs and helping students to develop skills in critical appraisal.

Interventions for preventing abuse in the elderly.

BACKGROUND: Maltreatment of older people (elder abuse) includes psychological, physical, sexual abuse, neglect and financial exploitation. Evidence suggests that 10% of older adults experience some form of abuse, and only a fraction of cases are actually reported or referred to social services agencies. Elder abuse is associated with significant morbidity and premature mortality. Numerous interventions have been implemented to address the issue of elder maltreatment. It is, however, unclear which interventions best serve to prevent or reduce elder abuse. OBJECTIVES: The objective of this review was to assess the effectiveness of primary, secondary and tertiary intervention programmes used to reduce or prevent abuse of the elderly in their own home, in organisational or institutional and community settings. The secondary objective was to investigate whether intervention effects are modified by types of abuse, types of participants, setting of intervention, or the cognitive status of older people. SEARCH METHODS: We searched 19 databases (AgeLine, CINAHL, Psycinfo, MEDLINE, Embase, Proquest Central, Social Services Abstracts , ASSIA, Sociological Abstracts, ProQuest Dissertations & Theses Global, Web of Science, LILACS, EPPI, InfoBase, CENTRAL, HMIC, Opengrey and Zetoc) on 12 platforms, including multidisciplinary disciplines covering medical, health, social sciences, social services, legal, finance and education. We also browsed related organisational websites, contacted authors of relevant articles and checked reference lists. Searches of databases were conducted between 30 August 2015 and 16 March 2016 and were not restricted by language. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised trials, and quasi-RCTs, before-and-after studies, and interrupted time series. Only studies with at least 12 weeks of follow-up investigating the effect of interventions in preventing or reducing abuse of elderly people and those who interact with the elderly were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the studies' risk of bias. Studies were categorised as: 1) education on elder abuse, 2) programmes to reduce factors influencing elder abuse, 3) specific policies for elder abuse, 4) legislation on elder abuse, 5) programmes to increase detection rate on elder abuse, 6) programmes targeted to victims of elder abuse, and 7) rehabilitation programmes for perpetrators of elder abuse. All studies were assessed for study methodology, intervention type, setting, targeted audience, intervention components and intervention intensity. MAIN RESULTS: The search and selection process produced seven eligible studies which included a total of 1924 elderly participants and 740 other people. Four of the above seven categories of interventions were evaluated by included studies that varied in study design. Eligible studies of rehabilitation programmes, specific policies for elder abuse and legislation on elder abuse were not found. All included studies contained a control group, with five of the seven studies describing the method of allocation as randomised. We used the Cochrane 'Risk of bias' tool and EPOC assessment criteria to assess risk of bias. The results suggest that risk of bias across the included body of research was high, with at least 40% of the included studies judged as being at high risk of bias. Only one study was judged as having no domains at high risk of bias, with two studies having two of 11 domains at high risk. One study was judged as being at high risk of bias across eight of 11 domains.All included studies were set in high-income countries, as determined by the World Bank economic classification (USA four, Taiwan one, UK two). None of the studies provided specific information or analysis on equity considerations, including by socio-economic disadvantage, although one study was described as being set in a housing project. One study performed some form of cost-effectiveness analysis on the implementation of their intervention programmes, although there were few details on the components and analysis of the costing.We are uncertain whether these interventions reduce the occurrence or recurrence of elder abuse due to variation in settings, measures and effects reported in the included studies, some of which were very small and at a high risk of bias (low- and very low-quality evidence).Two studies measured the occurrence of elder abuse. A high risk of bias study found a difference in the post-test scores (P value 0.048 and 0.18). In a low risk of bias study there was no difference found (adjusted odds ratio (OR) =0.48, 95% 0.18 to 1.27) (n = 214). For interventions measuring abuse recurrence, one small study (n = 16) reported no difference in post-test means, whilst another found higher levels of abuse reported for the intervention arms (Cox regression, combined intervention hazard ratio (HR) = 1.78, alpha level = 0.01).It is uncertain whether targeted educational interventions improve the relevant knowledge of health professionals and caregivers (very low-quality evidence), although they may improve detection of resident-to-resident abuse. The concept of measuring improvement in detection or reporting as opposed to measuring the occurrence or recurrence of abuse is complicated. An intervention of public education and support services aimed at victims may also improve rates of reporting, however it is unclear whether this was due to an increase in abuse recurrence or better reporting of abuse.The effectiveness of service planning interventions at improving the assessment and documentation of related domains is uncertain. Unintended outcomes were not reported in the studies. AUTHORS' CONCLUSIONS: There is inadequate trustworthy evidence to assess the effects of elder abuse interventions on occurrence or recurrence of abuse, although there is some evidence to suggest it may change the combined measure of anxiety and depression of caregivers. There is a need for high-quality trials, including from low- or middle-income countries, with adequate statistical power and appropriate study characteristics to determine whether specific intervention programmes, and which components of these programmes, are effective in preventing or reducing abuse episodes among the elderly. It is uncertain whether the use of educational interventions improves knowledge and attitude of caregivers, and whether such programmes also reduce occurrence of abuse, thus future research is warranted. In addition, all future research should include a component of cost-effectiveness analysis, implementation assessment and equity considerations of the specific interventions under review.

Partial breast irradiation for early breast cancer.

BACKGROUND: Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. SELECTION CRITERIA: Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. MAIN RESULTS: We included seven RCTs and studied 7586 women of the 8955 enrolled.Local recurrence-free survival appeared worse for women receiving PBI/APBI compared to WBRT (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.11 to 2.35; six studies, 6820 participants, low-quality evidence). Cosmesis (physician-reported) appeared worse with PBI/APBI (odds ratio (OR) 1.51, 95% CI 1.17 to 1.95, five studies, 1720 participants, low-quality evidence). Overall survival did not differ with PBI/APBI (HR 0.90, 95% CI 0.74 to 1.09, five studies, 6718 participants, high-quality evidence).Late radiation toxicity (subcutaneous fibrosis) appeared worse with PBI/APBI (OR 6.58, 95% CI 3.08 to 14.06, one study, 766 participants, moderate-quality evidence). Acute skin toxicity appeared reduced with PBI/APBI (OR 0.04, 95% CI 0.02 to 0.09, two studies, 608 participants). Telangiectasia (OR 26.56, 95% CI 3.59 to 196.51, 1 study, 766 participants) and radiological fat necrosis (OR 1.58, 95% CI 1.02 to 2.43, three studies, 1319 participants) appeared worse with PBI/APBI. Late skin toxicity (OR 0.21, 95% CI 0.01 to 4.39, two studies, 608 participants) and breast pain (OR 2.17, 95% CI 0.56 to 8.44, one study, 766 participants) appeared not to differ with PBI/APBI.'Elsewhere primaries' (new primaries in the ipsilateral breast) appeared more frequent with PBI/APBI (OR 3.97, 95% CI 1.51 to 10.41, three studies, 3009 participants).We found no clear evidence of a difference for the comparison of PBI/APBI with WBRT for the outcomes of: cause-specific survival (HR 1.08, 95% CI 0.73 to 1.58, five studies, 6718 participants, moderate-quality evidence), distant metastasis-free survival (HR 0.94, 95% CI 0.65 to 1.37, four studies, 3267 participants, moderate-quality evidence), relapse-free survival (HR 1.36, 95% CI 0.88 to 2.09, three studies, 3811 participants), loco-regional recurrence-free survival (HR 1.80, 95% CI 1.00 to 3.25, two studies, 3553 participants) or mastectomy rates (OR 1.20, 95% CI 0.77 to 1.87, three studies, 4817 participants, low-quality evidence). Compliance was met: more than 90% of the women in all studies received the RT they were assigned to receive. We found no data for the outcomes of costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: It appeared that local recurrence and 'elsewhere primaries' (new primaries in the ipsilateral breast) are increased with PBI/APBI (the difference was small), but we found no evidence of detriment to other oncological outcomes. It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Fraction size in radiation therapy for breast conservation in early breast cancer.

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an update of a Cochrane Review first published in 2008 and updated in 2009. OBJECTIVES: To assess the effect of altered radiation fraction size for women with early breast cancer who have had breast conserving surgery. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Register (23 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Jan 1996 to May 2015), EMBASE (Jan 1980 to May 2015), the WHO International Clinical Trials Registry Platform (ICTRP) search portal (June 2010 to May 2015) and ClinicalTrials.gov (16 April 2015), reference lists of articles and relevant conference proceedings. No language or publication constraints were applied. SELECTION CRITERIA: Randomised controlled trials of altered fraction size versus conventional fractionation for radiation therapy in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: Two authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: We studied 8228 women in nine studies. Eight out of nine studies were at low or unclear risk of bias. Altered fraction size (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not have a clinically meaningful effect on: local recurrence-free survival (Hazard Ratio (HR) 0.94, 95% CI 0.77 to 1.15, 7095 women, four studies, high-quality evidence), cosmetic outcome (Risk ratio (RR) 0.90, 95% CI 0.81 to 1.01, 2103 women, four studies, high-quality evidence) or overall survival (HR 0.91, 95% CI 0.80 to 1.03, 5685 women, three studies, high-quality evidence). Acute radiation skin toxicity (RR 0.32, 95% CI 0.22 to 0.45, 357 women, two studies) was reduced with altered fraction size. Late radiation subcutaneous toxicity did not differ with altered fraction size (RR 0.93, 95% CI 0.83 to 1.05, 5130 women, four studies, high-quality evidence). Breast cancer-specific survival (HR 0.91, 95% CI 0.78 to 1.06, 5685 women, three studies, high quality evidence) and relapse-free survival (HR 0.93, 95% CI 0.82 to 1.05, 5685 women, three studies, moderate-quality evidence) did not differ with altered fraction size. We found no data for mastectomy rate. Altered fraction size was associated with less patient-reported (P < 0.001) and physician-reported (P = 0.009) fatigue at six months (287 women, one study). We found no difference in the issue of altered fractionation for patient-reported outcomes of: physical well-being (P = 0.46), functional well-being (P = 0.38), emotional well-being (P = 0.58), social well-being (P = 0.32), breast cancer concerns (P = 0.94; 287 women, one study). We found no data with respect to costs. AUTHORS' CONCLUSIONS: We found that using altered fraction size regimens (greater than 2 Gy per fraction) does not have a clinically meaningful effect on local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance, late toxicity or patient-reported quality-of-life measures for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins.

Community wide interventions for increasing physical activity.

BACKGROUND: Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. OBJECTIVES: To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. SEARCH METHODS: We searched the Cochrane Public Health Group Segment of the Cochrane Register of Studies,The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, the British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORT Discus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.org; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA); the US Centre for Disease Control and Prevention (CDC) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were searched and we contacted experts in the field. The searches were updated to 16 January 2014, unrestricted by language or publication status. SELECTION CRITERIA: Cluster randomised controlled trials, randomised controlled trials, quasi-experimental designs which used a control population for comparison, interrupted time-series studies, and prospective controlled cohort studies were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised individuals from the same community were excluded. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted the data and assessed the risk of bias. Each study was assessed for the setting, the number of included components and their intensity. The primary outcome measures were grouped according to whether they were dichotomous (per cent physically active, per cent physically active during leisure time, and per cent physically inactive) or continuous (leisure time physical activity time (time spent)), walking (time spent), energy expenditure (as metabolic equivalents or METS)). For dichotomous measures we calculated the unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. For continuous measures we calculated percentage change from baseline, unadjusted and adjusted. MAIN RESULTS: After the selection process had been completed, 33 studies were included. A total of 267 communities were included in the review (populations between 500 and 1.9 million). Of the included studies, 25 were set in high income countries and eight were in low income countries. The interventions varied by the number of strategies included and their intensity. Almost all of the interventions included a component of building partnerships with local governments or non-governmental organisations (NGOs) (29 studies). None of the studies provided results by socio-economic disadvantage or other markers of equity. However, of those included studies undertaken in high income countries, 14 studies were described as being provided to deprived, disadvantaged or low socio-economic communities. Nineteen studies were identified as having a high risk of bias, 10 studies were unclear, and four studies had a low risk of bias. Selection bias was a major concern with these studies, with only five studies using randomisation to allocate communities. Four studies were judged as being at low risk of selection bias although 19 studies were considered to have an unclear risk of bias. Twelve studies had a high risk of detection bias, 13 an unclear risk and four a low risk of bias. Generally, the better designed studies showed no improvement in the primary outcome measure of physical activity at a population level.All four of the newly included, and judged to be at low risk of bias, studies (conducted in Japan, United Kingdom and USA) used randomisation to allocate the intervention to the communities. Three studies used a cluster randomised design and one study used a stepped wedge design. The approach to measuring the primary outcome of physical activity was better in these four studies than in many of the earlier studies. One study obtained objective population representative measurements of physical activity by accelerometers, while the remaining three low-risk studies used validated self-reported measures. The study using accelerometry, conducted in low income, high crime communities of USA, emphasised social marketing, partnership with police and environmental improvements. No change in the seven-day average daily minutes of moderate to vigorous physical activity was observed during the two years of operation. Some program level effect was observed with more people walking in the intervention community, however this result was not evident in the whole community. Similarly, the two studies conducted in the United Kingdom (one in rural villages and the other in urban London; both using communication, partnership and environmental strategies) found no improvement in the mean levels of energy expenditure per person per week, measured from one to four years from baseline. None of the three low risk studies reporting a dichotomous outcome of physical activity found improvements associated with the intervention.Overall, there was a noticeable absence of reporting of benefit in physical activity for community wide interventions in the included studies. However, as a group, the interventions undertaken in China appeared to have the greatest possibility of success with high participation rates reported. Reporting bias was evident with two studies failing to report physical activity measured at follow up. No adverse events were reported.The data pertaining to cost and sustainability of the interventions were limited and varied. AUTHORS' CONCLUSIONS: Although numerous studies have been undertaken, there is a noticeable inconsistency of the findings in the available studies and this is confounded by serious methodological issues within the included studies. The body of evidence in this review does not support the hypothesis that the multi-component community wide interventions studied effectively increased physical activity for the population, although some studies with environmental components observed more people walking.

Partial breast irradiation for early breast cancer.

BACKGROUND: Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. DATA COLLECTION AND ANALYSIS: Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials, graded the methodological quality using Cochrane's Risk of Bias tool and resolved any disagreements through discussion. MAIN RESULTS: We included four RCTs that had 2253 women. Two older trials examined RT techniques which do not reflect current practice and one trial had a short follow-up. We downgraded the quality of the evidence for our key outcomes due to risk of bias. Taken together with other GRADE recommendations, the quality of evidence for our outcomes was very low to low. For the comparison of partial breast irradiation/accelerated breast irradiation (PBI/APBI) with whole breast irradiation (WBRT), local recurrence-free survival appeared worse (Hazard Ratio (HR) 1.74, 95% confidence interval (CI) 1.23 to 2.45; three trials, 1140 participants, very low quality evidence). Cosmesis appeared improved with PBI/APBI in a single trial (OR 0.40, 95% CI 0.23 to 0.72; one trial, 241 participants, very low quality evidence), but late toxicity (telangiectasia OR 4.41, 95% CI 3.21 to 6.05; very low quality evidence, 708 participants) and subcutaneous fibrosis (OR 4.27, 95% CI 3.04 to 6.01; one trial, 710 participants, very low quality evidence) appeared increased in another trial. We found no clear evidence of a difference for the comparison of PBI/APBI versus WBRT for the outcomes of: overall survival (HR 0.99, 95% CI 0.83 to 1.18; three trials, 1140 participants, very low quality evidence), cause-specific survival (HR 0.95, 95% CI 0.74 to 1.22; two trials, 966 participants, low evidence quality), distant metastasis-free survival (HR 1.02, 95% CI 0.81 to 1.28; 1140 participants, low quality evidence), subsequent mastectomy rate (OR 0.20, 95% CI 0.01 to 4.21; 258 participants, low quality evidence) and relapse-free survival (HR 0.99, 95% CI 0.53 to 1.85; 258 participants, low quality evidence). We found no data for the outcomes of acute toxicity, new ipsilateral breast primaries, costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Interventions for erythropoietin-resistant anaemia in dialysis patients.

BACKGROUND: People living with end-stage kidney disease (ESKD) often develop anaemia. Erythropoiesis-simulating agents (ESAs) are often given to people living with ESKD to maintain haemoglobin at a level to minimise need for transfusion. However, about 5% to 10% of patients with ESKD exhibit resistance to ESAs, and observational studies have shown that patients requiring high doses of ESA are at increased risk of mortality. OBJECTIVES: This review aimed to study the effects of interventions for the treatment of ESA-resistant anaemia in people with ESKD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE for randomised controlled trials (RCT) that involved participants with ESKD on dialysis or who were pre-dialysis patients with chronic kidney disease (stage 5). Date of last search: April 2013. SELECTION CRITERIA: ESA resistance was defined as failure to achieve or maintain haemoglobin/haematocrit levels within the desired target range despite appropriate ESA doses (erythropoietin ≥ 450 U/kg/wk intravenously or ≥ 300 U/kg/wk subcutaneously; darbepoetin ≥ 1.5 µg/kg/wk) in people who were not nutritionally deficient, or who had haematological or bleeding disorders. Extended inclusion criteria for ESA hyporesponsive state were: erythropoietin dose ≥ 300 U/kg/wk and ≥ 150 U/kg/wk for intravenous administration; or ≥ 200 U/kg/wk and ≥ 100 U/kg/wk for subcutaneous administration; or darbepoetin dose ≥ 1.0 µg/kg/wk). DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Titles and abstracts of 521 records were screened, of which we reviewed 99 from the full text. Only two studies matched our inclusion criteria. One study compared intravenous vitamin C versus no study medication for six months in 42 ESKD patients on haemodialysis who required intravenous erythropoietin (dose ≥ 450 U/kg/wk). The other included study compared high-flux dialyser versus low-flux dialyser for six months in 48 haemodialysis patients who required subcutaneous erythropoietin (dose ≥ 200 U/kg/wk). Because interventions differed, data could not be combined for quantitative meta-analysis. AUTHORS' CONCLUSIONS: There was inadequate evidence identified to inform recommendation of any intervention to ameliorate ESA hyporesponsiveness. Adequately powered RCTs are required to establish the safety and efficacy of interventions to improve responsiveness to ESA therapy.

Sequencing of chemotherapy and radiotherapy for early breast cancer.

BACKGROUND: After surgery for localised breast cancer, radiotherapy (RT) improves both local control and breast cancer-specific survival. In patients at risk of harbouring micro-metastatic disease, adjuvant chemotherapy (CT) improves 15-year survival. However, the best sequence of administering these two types of adjuvant therapy for early-stage breast cancer is unclear. OBJECTIVES: To determine the effects of different sequencing of adjuvant CT and RT for women with early breast cancer. SEARCH METHODS: An updated search was carried out in the Cochrane Breast Cancer Group's Specialised Register (20 May 2011), MEDLINE (14 December 2011), EMBASE (20 May 2011) and World Health Organization (WHO) International Clinical Trials Registry Platform (20 May 2011). Details of the search strategy and methods of coding for the Specialised Register are described in the Group's module in The Cochrane Library. We extracted studies that had been coded as 'early', 'chemotherapy' and 'radiotherapy'. SELECTION CRITERIA: We included randomised controlled trials evaluating different sequencing of CT and RT. DATA COLLECTION AND ANALYSIS: We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included trials. We derived odds ratios (OR) and hazard ratios (HR) from the available numerical data. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments. MAIN RESULTS: Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for local recurrence-free survival, overall survival, relapse-free survival and metastasis-free survival based on 1166 randomised women in three trials. Concurrent chemoradiation increased anaemia (OR 1.54; 95% confidence interval (CI) 1.10 to 2.15), telangiectasia (OR 3.85; 95% CI 1.37 to 10.87) and pigmentation (OR 15.96; 95% CI 2.06 to 123.68). Treated women did not report worse cosmesis with concurrent chemoradiation but physician-reported assessments did (OR 1.14; 95% CI 0.42 to 3.07). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), RT before CT was associated with an increased risk of neutropenic sepsis (OR 2.96; 95% CI 1.26 to 6.98) compared with CT before RT, but other measures of toxicity did not differ. AUTHORS' CONCLUSIONS: The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.

Assessment of applicability and transferability of evidence-based antenatal interventions to the Australian indigenous setting.

There is a need for public health interventions to be based on the best available evidence. Unfortunately, well-conducted studies from settings similar to that in which an intervention is to be implemented are often not available. Therefore, health practitioners are forced to make judgements about proven effective interventions in one setting and their suitability to make a difference in their own setting. The framework of Wang et al. has been proposed to help with this process. This paper provides a case study on the application of the framework to a decision-making process regarding antenatal care in Aboriginal and Torres Strait Islander communities in Queensland. This method involved undertaking a systematic search of the current available evidence, then conducting a second literature search to determine factors that may affect the applicability and transferability of these interventions into these communities. Finally, in consideration of these factors, clinical judgement decisions on the applicability and transferability of these interventions were made. This method identified several interventions or strategies for which there was evidence of improving antenatal care or outcomes. By using the framework, we concluded that several of these effective interventions would be feasible in Aboriginal and Torres Strait Islander communities within Queensland.

Adjuvant radiotherapy following radical prostatectomy for prostate cancer.

BACKGROUND: Men who have a radical prostatectomy (RP) for prostate cancer that does not involve lymph nodes, but extends beyond the prostate capsule into the seminal vesicles or to surgical margins, are at increased risk of relapse. In men with these high risk factors, radiotherapy (RT) directed at the prostate bed after surgery may reduce this risk, and be curative. OBJECTIVES: To evaluate the effect of adjuvant RT following RP for prostate cancer in men with high risk features compared with RP. SEARCH METHODS: We searched the Cochrane Prostatic Diseases and Urological Cancers Specialised Register (23 February 2011), the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE (January 1966 to February 2011), PDQ® (Physician Data Query) trial registry databases for ongoing studies (2 November 2010), reference lists from selected studies and reviews, and handsearched relevant conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing RP followed by RT with RP alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion and bias and extracted data for analysis. Authors were contacted to clarify data and obtain missing information. MAIN RESULTS: We found three RCTs involving 1815 men. Adjuvant RT following prostatectomy did not affect overall survival at 5 years (RD (risk difference) 0.00; 95% CI -0.03 to 0.03), but improved survival at 10 years (RD -0.11; 95% CI -0.20 to -0.02). Adjuvant RT did not improve prostate cancer-specific mortality at 5 years (RD -0.01; 95% CI -0.03 to 0.00). Adjuvant RT did not reduce metastatic disease at 5 years (RD -0.00; 95% CI -0.04 to 0.03), but reduced it at 10 years (RD -0.11; 95% CI -0.20 to -0.01). It improved local control at 5 and 10 years (RD -0.10; 95% CI -0.13 to -0.06 and RD -0.14; 95% CI -0.21 to -0.07, respectively), and biochemical progression-free survival at 5 years and 10 years (RD -0.16; 95% CI -0.21 to -0.11 and RD -0.29; 95% CI -0.39 to -0.19, respectively). There were no data for clinical disease-free survival. Adjuvant RT increased acute and late gastrointestinal toxicity [do you have the rd for this?], urinary stricture (RD 0.05; 95% CI 0.01 to 0.09) and incontinence (RD 0.04; 95% CI 0.01 to 0.08). It did not increase erectile dysfunction or degrade quality of life (RD 0.01; 95% CI -0.06 to -0.26), but with limited data. AUTHORS' CONCLUSIONS: Adjuvant RT after RP improves overall survival and reduces the rate of distant metastases, but these effects are only evident with longer follow up. At 5 and 10 years it improves local control and reduces the risk of biochemical failure, although the latter is not a clinical endpoint. Moderate or severe acute and late toxicity is minimal. There is an increased risk of urinary stricture and incontinence, but no detriment to quality of life, based on limited data. Given that the majority of men who have undergone a RP have a longer life expectancy, radiotherapy should be considered for those with high-risk features following radical prostatectomy. The optimal timing is unclear.

Community wide interventions for increasing physical activity.

BACKGROUND: Multi-strategic community wide interventions for physical activity are increasingly popular but their ability to achieve population level improvements is unknown. OBJECTIVES: To evaluate the effects of community wide, multi-strategic interventions upon population levels of physical activity. SEARCH STRATEGY: We searched the Cochrane Public Health Group Specialised Register, The Cochrane Library, MEDLINE, MEDLINE in Process, EMBASE, CINAHL, LILACS, PsycINFO, ASSIA, The British Nursing Index, Chinese CNKI databases, EPPI Centre (DoPHER, TRoPHI), ERIC, HMIC, Sociological Abstracts, SPORTDiscus, Transport Database and Web of Science (Science Citation Index, Social Sciences Citation Index, Conference Proceedings Citation Index). We also scanned websites of the EU Platform on Diet, Physical Activity and Health; Health-Evidence.ca; the International Union for Health Promotion and Education; the NIHR Coordinating Centre for Health Technology (NCCHTA) and NICE and SIGN guidelines. Reference lists of all relevant systematic reviews, guidelines and primary studies were followed up. We contacted experts in the field from the National Obesity Observatory Oxford, Oxford University; Queensland Health, Queensland University of Technology, the University of Central Queensland; the University of Tennessee and Washington University; and handsearched six relevant journals. The searches were last updated to the end of November 2009 and were not restricted by language or publication status. SELECTION CRITERIA: Cluster randomised controlled trials, randomised controlled trials (RCT), quasi-experimental designs which used a control population for comparison, interrupted time-series (ITS) studies, and prospective controlled cohort studies (PCCS) were included. Only studies with a minimum six-month follow up from the start of the intervention to measurement of outcomes were included. Community wide interventions had to comprise at least two broad strategies aimed at physical activity for the whole population. Studies which randomised individuals from the same community were excluded. DATA COLLECTION AND ANALYSIS: At least two review authors independently extracted the data and assessed the risk of bias of each included study. Non-English language papers were reviewed with the assistance of an epidemiologist interpreter. Each study was assessed for the setting, the number of included components and their intensity. Outcome measures were grouped according to whether they were dichotomous (physically active, physically active during leisure time and sedentary or physically inactive) or continuous (leisure time physical activity, walking, energy expenditure). For dichotomous measures we calculated the unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. For continuous measures we calculated net percentage change from baseline, unadjusted and adjusted risk difference, and the unadjusted and adjusted relative risk. MAIN RESULTS: After the selection process had been completed 25 studies were included in the review. Of the included studies, 19 were set in high income countries, using the World Bank economic classification, and the remaining six were in low income countries. The interventions varied by the number of strategies included and their intensity. Almost all of the interventions included a component of building partnerships with local governments or non-governmental organisations (NGOs) (22 studies). None of the studies provided results by socio-economic disadvantage or other markers of equity consideration. However of those included studies undertaken in high income countries, 11 studies were described by the authors as being provided to deprived, disadvantaged, or low socio-economic communities.Fifteen studies were identified as having a high risk of bias, 10 studies were unclear, and no studies had a low risk of bias. Selection bias was a major concern with these studies, with only one study using randomisation to allocate communities (Simon 2008). No studies were judged as being at low risk of selection bias although 16 studies were considered to have an unclear risk of bias. Eleven studies had a high risk of detection bias, 10 with an unclear risk and four with no risk. Assessment of detection bias included an assessment of the validity of the measurement tools and quality of outcome measures. The effects reported were inconsistent across the studies and the measures. Some of the better designed studies showed no improvement in measures of physical activity. Publication bias was evident. AUTHORS' CONCLUSIONS: Although numerous studies have been undertaken, there is a noticeable inconsistency of the findings of the available studies and this is confounded by serious methodological issues within the included studies. The body of evidence in this review does not support the hypothesis that multi-component community wide interventions effectively increase population levels of physical activity. There is a clear need for well-designed intervention studies and such studies should focus on the quality of the measurement of physical activity, the frequency of measurement and the allocation to intervention and control communities.

Fraction size in radiation treatment for breast conservation in early breast cancer.

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an updated version of the original Cochrane Review published in Issue 3, 2008. OBJECTIVES: To determine the effect of altered radiation fraction size on outcomes for women with early breast cancer who have undergone breast conserving surgery. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE and the WHO ICTRP search portal to June 2009, reference lists of articles and relevant conference proceedings. We applied no language constraints. SELECTION CRITERIA: Randomised controlled trials of unconventional versus conventional fractionation in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: The authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: Four trials reported on 7095 women. The women were highly selected: tumours were node negative and 89.8% were smaller than 3 cm. Where the breast size was known, 87% had small or medium breasts. The studies were of low to medium quality. Unconventional fractionation (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not affect: (1) local recurrence risk ratio (RR) 0.97 (95% CI 0.76 to 1.22, P = 0.78), (2) breast appearance RR 1.17 (95% CI 0.98 to 1.39, P = 0.09), (3) survival at five years RR 0.89 (95% CI 0.77 to 1.04, P = 0.16). Acute skin toxicity was decreased with unconventional fractionation: RR 0.21 (95% CI 0.07 to 0.64, P = 0.007). AUTHORS' CONCLUSIONS: Two new studies have been published since the last version of the review, altering our conclusions. We have evidence from four low to medium quality randomised trials that using unconventional fractionation regimens (greater than 2 Gy per fraction) does not affect local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance or late toxicity for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins. Long-term follow up (> 5 years) is available for a small proportion of the patients randomised. Longer follow up is required for a more complete assessment of the effect of altered fractionation.

Fraction size in radiation treatment for breast conservation in early breast cancer.

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conservation. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. OBJECTIVES: To assess the effects of altered fraction size on women with early breast cancer who have undergone breast conserving surgery. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register (June 2006), MEDLINE (November 2006), EMBASE (November 2006), reference lists for articles, and relevant conference proceedings. No language constraints were applied. SELECTION CRITERIA: Randomised controlled trials of unconventional versus conventional fractionation in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: Data extraction was performed independently by the authors with disagreements resolved by discussion. Missing data was sought by contacting the authors concerned. MAIN RESULTS: Two trials were included and reported on 2644 women. The women were highly selected with node negative tumours smaller than 5 cm and negative pathological margins; 46% of the women had a cup separation size of less than 25 cm. The studies were of high quality. Data for local recurrence and breast appearance were not available in a form which could be combined. Unconventional fractionation (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not appear to affect: (1) local-recurrence free survival (absolute difference 0.4%, 95% CI -1.5% to 2.4%), (2) breast appearance (risk ratio (RR) 1.01, 95% CI 0.88 to 1.17; P = 0.86), (3) survival at five years (RR 0.97, 95% CI 0.78 to 1.19; P = 0.75), (4) late skin toxicity at five years (RR 0.99, 95% CI 0.44 to 2.22; P = 0.98, or (5) late radiation toxicity in sub-cutaneous tissue (RR 1.0, 95% CI 0.78 to 1.28; P = 0.99). AUTHORS' CONCLUSIONS: We have evidence from two high quality randomised trials that the use of unconventional fractionation regimes (greater than 2 Gy per fraction) does not affect breast appearance or toxicity and does not seem to affect local recurrence for selected women treated with breast conserving therapy. These are women with node negative tumours smaller than 5 cm and negative pathological margins. Two new trials have been published in March 2008. Their results are consistent with our findings. The results of these trials will be incorporated in the next update of this review.