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ObjectiveTo investigate the prognostic efficacy of lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in node-positive cardia gastric adenocarcinoma (CGA).DesignA registry-based retrospective cohort study.SettingPatients diagnosed with node-positive CGA in the Surveillance, Epidemiology, and End Results database from 2010 to 2015.ParticipantsA total of 1038 patients were enrolled and randomly assigned (7:3) to the training set (n=723) or validating set (n=315).Primary outcome measureCancer-specific survival (CSS).ResultsThe baseline characteristics of the training and validation sets were similar. Based on the optimal cut-off values, LNR was classified into low (0.33) groups; LODDS was also classified into low (−0.65) groups. CSS was significantly different across LNR and LODDS subgroups. The Harrell concordance index of the N stage was lower than that of the LNR or LODDS. The Akaike information criterion of the N stage was higher than that of the LNR or LODDS. Independent predictors included race, T stage, M stage and LNR (or LODDS), and they were incorporated into nomograms for 1-year, 2-year and 5-year CSS prediction. Calibration plots showed satisfactory results for internal and external validity of the nomogram.ConclusionsLNR and LODDS staging methods have better prognostic efficacy than the traditional N staging method in CGA with node metastasis. Moreover, the two values are promising substitutes for N staging in nomogram development when other independent prognostic factors are incorporated.

IntroductionAutism spectrum conditions (ASC) develop early in life and are thought to last a lifetime. However, ASC research has two major knowledge gaps that hinder progression in understanding the concept of ASC and in providing proper support for autistic adults: (1) the majority of knowledge about ASC mainly stems from childhood studies so little is known about older autistic adults and (2) while it is broadly recognised that ASC is a heterogeneous condition, we do not yet understand the differences in trajectories leading to their future outcome. We aim to fill both knowledge gaps.Methods and analysisA multistage overlapping cohort design assessing (cognitive) ageing in ASC is designed to obtain an accelerated longitudinal data set. Data, including a multitude of questionnaires, diagnostics and cognitive tests, are collected over four waves within a 10-year time frame. This will provide information regarding actual changes in quality of life, co-occurring health conditions and cognition as well as the possibility to test external validity and temporal stability in newly formed behavioural subtypes. Participants consist of three groups of adults aged 20–90 years: (1) with a clinical diagnosis of ASC, (2) with a clinical diagnosis of attention deficit hyperactivity disorder (ADHD) but no ASC, (3) no ASC/ADHD (ie, comparison group). The sample size differs between waves and instruments. Detailed analysis plans will be preregistered in AsPredicted or at the Open Science Framework.Ethics and disseminationEthical approval for this study was obtained from the ethical review board of the Department of Psychology of the University of Amsterdam (wave 1 2011-PN-1952 and 2013-PN-2668, wave 2 2015-BC-4270, waves 3 and 4 2018-BC-9285). In line with the funding policies of the grant organisation funding this study, future papers will be published open access.

ObjectiveTo determine whether assessment tools for non-randomised studies (NRS) address critical elements that influence the validity of NRS findings for comparative safety and effectiveness of medications.DesignSystematic review and Delphi survey.Data sourcesWe searched PubMed, Embase, Google, bibliographies of reviews and websites of influential organisations from inception to November 2019. In parallel, we conducted a Delphi survey among the International Society for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group to identify key methodological challenges for NRS of medications. We created a framework consisting of the reported methodological challenges to evaluate the selected NRS tools.Study selectionChecklists or scales assessing NRS.Data extractionTwo reviewers extracted general information and content data related to the prespecified framework.ResultsOf 44 tools reviewed, 48% (n=21) assess multiple NRS designs, while other tools specifically addressed case–control (n=12, 27%) or cohort studies (n=11, 25%) only. Response rate to the Delphi survey was 73% (35 out of 48 content experts), and a consensus was reached in only two rounds. Most tools evaluated methods for selecting study participants (n=43, 98%), although only one addressed selection bias due to depletion of susceptibles (2%). Many tools addressed the measurement of exposure and outcome (n=40, 91%), and measurement and control for confounders (n=40, 91%). Most tools have at least one item/question on design-specific sources of bias (n=40, 91%), but only a few investigate reverse causation (n=8, 18%), detection bias (n=4, 9%), time-related bias (n=3, 7%), lack of new-user design (n=2, 5%) or active comparator design (n=0). Few tools address the appropriateness of statistical analyses (n=15, 34%), methods for assessing internal (n=15, 34%) or external validity (n=11, 25%) and statistical uncertainty in the findings (n=21, 48%). None of the reviewed tools investigated all the methodological domains and subdomains.ConclusionsThe acknowledgement of major design-specific sources of bias (eg, lack of new-user design, lack of active comparator design, time-related bias, depletion of susceptibles, reverse causation) and statistical assessment of internal and external validity is currently not sufficiently addressed in most of the existing tools. These critical elements should be integrated to systematically investigate the validity of NRS on comparative safety and effectiveness of medications.Systematic review protocol and registrationhttps://osf.io/es65q.

ObjectivesTo systematically analyse the effect of pharmacological treatment of hypertension (HTN) on cognitive decline in older adults.MethodsRandomised, placebo-controlled trials with a prespecified quantitative outcome of cognition and a pharmacological intervention for at least 12 months to treat HTN in older adults (>60 years). Our primary outcome was change in cognition with pharmacological treatment of HTN. Standardised mean difference (SMD) was used to analyse different outcomes reported in the selected studies. We searched PubMed CENTRAL and the Cochrane Library from inception to 6 July 2020. Two independent reviewers assessed trial quality and extracted data. Internal and external validity of the studies was assessed.ResultsNine randomised controlled trials with 34 994 participants were included in the final analysis. The net SMD for change in cognition was −0.049 (CI: −0.078 to −0.019) indicating that treatment of HTN decreased cognitive decline. Heterogeneity was low with an I² of 6%.DiscussionCurrent evidence does not indicate worsening of cognition with treatment of HTN. Treatment of HTN in older adults may reduce cognitive decline. These results have important implications in clinical management of patients at risk for dementia.PROSPERO registration numberCRD42020139750.

IntroductionOne of the main limitations that can be observed after acquired brain injury (ABI) is the alteration of the awareness of the deficits that can occur in the cognitive skills necessary for performing activities of daily living (ADL). According to the Dynamic Comprehensive Model of Awareness (DCMA), consciousness is composed of offline component, which contains the information stored about characteristics of the tasks and stable beliefs about one’s own capabilities and online awareness, which is activated in the context of the performance of a specific task. The main objective of this project was to generate and validate a detailed cognitive assessment protocol within the context of ADL to evaluate the components of DCMA.Methods and analysisThe proposed protocol consists of two ecological tools: The Cog-Awareness ADL Scale to measure offline component and the Awareness ADL-task: Basic and Instrumental ADL performance-based test to measure online awareness. The aim is to identify the presence of cognitive deficits and anosognosia in patients with ABI within the context of everyday life activities. These two measures will be administered to a group of patients with ABI. In addition, these participants will complete another series of classic tests on anosognosia and cognitive functions in order to find the convergent validity of the two tests proposed in this protocol. The external validity of the Cog-Awareness ADL Scale and the relationships between awareness components within the same ADL domain will be also analysed.Ethics and disseminationThis study was approved by the Ethics Committee of Biomedical Research of Andalusia, on 13 January /2017 (Proceeding 1/2017). All participants are required to provide written informed consent. The findings from this will be disseminated via scientific publication.Trial registration numberNCT03712839.

ObjectiveTo determine the feasibility and optimal design of a randomised controlled trial (RCT) of Seizure First Aid Training For Epilepsy (SAFE).DesignPilot RCT with embedded microcosting.SettingThree English hospital emergency departments (EDs).ParticipantsPatients aged ≥16 with established epilepsy reporting ≥2 ED visits in the prior 12 months and their significant others (SOs).InterventionsPatients (and their SOs) were randomly allocated (1:1) to SAFE plus treatment-as-usual (TAU) or TAU alone. SAFE is a 4-hour group course.Main outcome measuresTwo criteria evaluated a definitive RCT’s feasibility: (1) ≥20% of eligible patients needed to be consented into the pilot trial; (2) routine data on use of ED over the 12 months postrandomisation needed securing for ≥75%. Other measures included eligibility, ease of obtaining routine data, availability of self-report ED data and comparability, SAFE’s effect and intervention cost.ResultsOf ED attendees with a suspected seizure, 424 (10.6%) patients were eligible; 53 (12.5%) patients and 38 SOs consented. Fifty-one patients (and 37 SOs) were randomised. Routine data on ED use at 12 months were secured for 94.1% patients. Self-report ED data were available for 66.7% patients. Patients reported more visits compared with routine data. Most (76.9%) patients randomised to SAFE received it and no related serious adverse events occurred. ED use at 12 months was lower in the SAFE+TAU arm compared with TAU alone, but not significantly (rate ratio=0.62, 95% CI 0.33 to 1.17). A definitive trial would need ~674 patient participants and ~39 recruitment sites. Obtaining routine data was challenging, taking ~8.5 months.ConclusionsIn satisfying only one predetermined ‘stop/go’ criterion, a definitive RCT is not feasible. The low consent rate in the pilot trial raises concerns about a definitive trial’s finding’s external validity and means it would be expensive to conduct. Research is required into how to optimise recruitment from the target population.Trial registration numberISRCTN13871327

ObjectivesTransparent reporting of trials is necessary to assess their internal and external validity. Currently, little is known about the quality of reporting in antibiotics trials. Our study investigates the reporting of adverse events, conflicts of interest and funding information in trials of penicillins, cephalosporins and macrolides.DesignA secondary analysis of trials included in a convenience sample of three systematic reviews.MethodsAll randomised controlled trials included in the systematic reviews were included, although duplicates were removed. Eligible trials compared the specified antibiotics to placebo, for any indication. Author pairs independently extracted the data on reporting of adverse events from parent reviews, and data on funding and conflict of interest information from the trial reports. We calculated the overall proportion of trials reporting adverse events, conflict of interest information and funding information, and their proportion before and after the publication of the Consolidated Standards of Reporting Trials (CONSORT) 2001 Statement.ResultsWe included 432 trials. Overall, 62% of trials reported adverse events of any kind, although reporting of deaths or antibiotic resistance was less frequent (20% and 37%, respectively). Conflict-of-interest information was provided in 26% of the trials, and funding information was provided in 66% of the trials. There was no significant difference in reporting of adverse events before and after the publication of CONSORT 2001 Statement (62% vs 62%, p=0.92). Conflict of interest statements were provided more frequently (2% vs 55%, pConclusionsInformation about adverse events, conflict of interest and funding, remains under-reported in trials of antibiotics.

IntroductionSelf-efficacy refers to individuals’ confidence in their ability to perform relevant tasks to accomplish desired goals. This is independent of their actual abilities. In people with multiple sclerosis (MS), self-efficacy has been shown to powerfully influence motivation and health-related behaviour, such as adherence to prescribed treatment or physical activity. So far, a rigorously tested German language self-efficacy questionnaire for people with MS is missing.MethodsThe purpose of this study is to translate the original Unidimensional Self-Efficacy Scale for Multiple Sclerosis (USE-MS) into German and to validate the German USE-MS (USE-MS-G). Based on Bandura’s concept of self-efficacy and international guidelines for questionnaire development, the patient-led development of the pre-final German version will involve a forward–backward translation process, synthesis of translations, expert committee review and consensus with the original test developers. At two centres in Tyrol, Austria, content and face validity and cultural adaption for Austria will be established using face-to-face semistructured cognitive interviews of 30 people with MS (PwMS). A further 292 PwMS with minimal to severe disability will be tested at two timepoints to validate the USE-MS-G.ResultsMixed methods analyses will be applied. Interviews will be transcribed and analysed employing qualitative content analysis. External validity will be explored using Spearman’s Rank correlation coefficients of the USE-MS-G with the 13-item Resilience Scale, General Self-Efficacy Scale, Multiple Sclerosis International Quality of Life questionnaire, Hospital Anxiety and Depression Scale and MS-specific Neurological Fatigue Index. Test–retest reliability, internal consistency and floor and ceiling effects will be evaluated. Internal validity will be examined using Rasch analysis.Ethics and disseminationEthical approval was received from the Ethics Committee of the Medical University of Innsbruck, Austria (reference number EK1260/2018; 13.12.2018). Results from this study will be disseminated to the participants and MS Societies, and to clinicians and researchers through peer-reviewed publications and conferences.Study registrationISRCTN Registry; trial ID ISRCTN14843579; prospectively registered on 02. 01. 2019; http://www.isrctn.com/ISRCTN14843579

IntroductionThere are more people living with dementia in low- and middle-income countries (LMICs) than in high-income countries. Evidence-based interventions to improve the lives of people living with dementia and their carers are needed, but a systematic mapping of methodologically robust studies in LMICs and synthesis of the effectiveness of dementia interventions in these settings is missing.Methods and analysisA systematic review and meta-analysis will be conducted to answer the question: Which dementia interventions were shown to be effective in LMICs and how do they compare to each other? Electronic database searches (MEDLINE, EMBASE, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Cochrane CENTRAL, Social Care Online, BASE, MODEM Toolkit, Cochrane Database of Systematic Reviews) will be complemented by hand searching of reference lists and local knowledge of existing studies from an international network of researchers in dementia from LMICs. Studies will be eligible for inclusion if they were published between 2008 and 2018, conducted in LMICs and evaluated the effectiveness of a dementia intervention using a study design that supports causal inference of the treatment effect. We will include both randomised and non-randomised studies due to an anticipated low number of well-conducted randomised trials in LMICs and potentially greater external validity of non-randomised studies conducted in routine care settings. In addition to narrative synthesis of the interventions, feasibility of pairwise and network meta-analyses will be explored to obtain pooled effects of relative treatment effects.Ethics and disseminationSecondary analysis of published studies, therefore no ethics approval required. Planned dissemination channels include a peer-reviewed publication as well as a website, DVD and evidence summaries.Prospero registration numberCRD42018106206.

ObjectivesTo validate the self-reported diagnoses of gynaecological and breast cancers in a nationwide prospective cohort study of nursing professionals: the Japan Nurses’ Health Study (JNHS).Design and settingRetrospective analysis of the JNHS.Participants and measuresData were reviewed for 15 717 subjects. The mean age at baseline was 41.6±8.3 years (median: 41), and the mean follow-up period was 10.5±3.8 years (median: 12). Participants are regularly mailed a follow-up questionnaire once every 2 years. Respondents who self-reported a positive cancer diagnosis were sent an additional confirmation questionnaire and contacted the diagnosing facility to confirm the diagnosis based on medical records. A review panel of experts verified the disease status. Regular follow-up, confirmation questionnaires and expert review were validated for their positive predictive value (PPV) and negative predictive value (NPV).ResultsNew incidences were verified in 37, 47, 26 and 300 cervical, endometrial, ovarian and breast cancer cases, respectively. The estimated incidence rates were 22.0, 25.4, 13.8 and 160.4 per 100 000 person-years. These were comparable with those of national data from regional cancer registries in Japan. For regular follow-up, the corresponding PPVs for cervical, endometrial, ovarian and breast cancer were 16.9%, 54.2%, 45.1% and 81.4%, and the NPVs were 100%, 99.9%, 99.9% and 99.9%, respectively. Adding the confirmation questionnaire improved the PPVs to 31.5%, 88.9%, 76.7% and 99.9%; the NPVs were uniformly 99.9%. Expert review yielded PPVs and NPVs that were all ~100%.ConclusionsGynaecological cancer cannot be accurately assessed by self-reporting alone. Additionally, the external validity of cancer incidence in this cohort was confirmed.

IntroductionQuality of reporting refers to how published articles communicate how the research was done and what was found. Gaps and imprecisions of reporting hamper the assessment of the methodological quality and internal and external validity. The CONsolidated Standards of Reporting Trials (CONSORT) are a set of evidence-based recommendations of the minimum elements to be included in the reporting of randomised controlled trials (RCTs) to ensure a complete and transparent account of what was done, how it was done and what was found. Few studies have been conducted on the impact of CONSORT on RCTs published in Latin American and Spanish journals. We aim to assess the reporting quality of RCTs of three clinical specialities published in Spanish and Latin American journals, as well as to assess changes over time and associations of quality with journal and country indicators.Methods and analysisWe will conduct a systematic survey of all RCTs published in Spanish-language journals in three clinical fields (dentistry, neurology and geriatrics) from 1990 to 2018. We will include RCTs from previous work that has identified all RCTs on these medical fields published in Spain and Latin America. We will update this work via handsearching of relevant journals. Assessment of quality of reporting will be conducted independently and in duplicate using the CONSORT 2010 Statement. We will also extract journal and country indicators. We will conduct descriptive statistics and secondary analyses considering the year, country, and journal of publication, among others.Ethics and disseminationThe Universidad de Santiago de Chile’s ethics committee approved the protocol. We will disseminate the results of this work in peer-reviewed scientific journals and conference proceedings. We expect to raise awareness among researchers, journal editors and funders on the importance of training in reporting guidelines and using them from the inception of RCT protocols.

ObjectiveTo describe the distribution of perfusion index (PI) in asymptomatic newborns at 24 hours of life when screening for critical congenital heart disease (CCHD) using an automated data selection method.DesignThis is a retrospective observational study.SettingNewborn nursery in a California public hospital with ~3500 deliveries annually.MethodsWe developed an automated programme to select the PI values from CCHD screens. Included were term and late preterm infants who were screened for CCHD from November 2013 to January 2014 and from May 2015 to July 2015. PI measurements were downloaded every 2 s from the pulse oximeter and median PI were calculated for each oxygen saturation screen in our cohort.ResultsWe included data from 2768 oxygen saturation screens. Each screen had a median of 29 data points (IQR 17 to 49). The median PI in our study cohort was 1.8 (95% CI 1.8 to 1.9) with IQR 1.2 to 2.7. The median preductal PI was significantly higher than the median postductal (1.9 vs 1.8, p=0.03) although this difference may not be clinically significant.ConclusionUsing an automated data selection method, the median PI in asymptomatic newborns at 24 hours of life is 1.8 with a narrow IQR of 1.2 to 2.7. This automated data selection method may improve accuracy and precision compared with manual data collection method. Further studies are needed to establish external validity of this automated data selection method and its clinical application for CCHD screening.

ObjectiveThe proliferation of studies using motivational signs to promote stair use continues unabated, with their oft-cited potential for increasing population-level physical activity participation. This study examined all stair use promotional signage studies since 1980, calculating pre-estimates and post-estimates of stair use. The aim of this project was to conduct a sequential meta-analysis to pool intervention effects, in order to determine when the evidence base was sufficient for population-wide dissemination.DesignUsing comparable data from 50 stair-promoting studies (57 unique estimates) we pooled data to assess the effect sizes of such interventions.ResultsAt baseline, median stair usage across interventions was 8.1%, with an absolute median increase of 2.2% in stair use following signage-based interventions. The overall pooled OR indicated that participants were 52% more likely to use stairs after exposure to promotional signs (adjusted OR 1.52, 95% CI 1.37 to 1.70). Incremental (sequential) meta-analyses using z-score methods identified that sufficient evidence for stair use interventions has existed since 2006, with recent studies providing no further evidence on the effect sizes of such interventions.ConclusionsThis analysis has important policy and practice implications. Researchers continue to publish stair use interventions without connection to policymakers' needs, and few stair use interventions are implemented at a population level. Researchers should move away from repeating short-term, small-scale, stair sign interventions, to investigating their scalability, adoption and fidelity. Only such research translation efforts will provide sufficient evidence of external validity to inform their scaling up to influence population physical activity.

ObjectiveDiagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients.DesignProspective cohort study.SettingGeneral medicine departments of three teaching hospitals in Japan.ParticipantsA total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016.Main outcome measuresThe reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model.ResultsAmong the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0–5.3), negative likelihood ratio of 0.4 (0.2–0.7) and OR of 7.7 (3.0–19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA.ConclusionsInformation on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly.

ObjectivesThis article reviews the applicability of a customised version of the Appropriateness Evaluation Protocol (AEP) to evaluate the magnitude of inappropriate hospitalisations in two regions of Ukraine.Data and methodsThe original AEP was modified to develop a customised tool, which included criteria for the appropriateness of hospitalisation and duration of inpatient stay. The customisation of the tool followed the Delphi procedure. We randomly selected 381 medical records to test the feasibility and reliability of the method and 800 medical records to evaluate the scope of inappropriate hospitalisations. We used descriptive and analytical statistics, receiver operating characteristic curve analysis and Cohen's kappa to check the consistency between the findings of primary reviewers and experts.ResultWe observed high levels of agreement in conclusions of primary reviewers (reference standard) and experts during testing of the reliability and validity of the method. The external validity check showed that the use of the tool by different experts provided high accuracy: 95.1 sensitivity, 76.6 specificity and area under ROC-curve (AUC)=0.948 (рκ) indicated agreement in expert evaluations of 0.915 (95% СІ 0.799 to 1.000) and 0.812 (95% СІ 0.749 to 0.875), respectively.We found that over one-third of admissions (38.1%; 95% СІ 33.9 to 43.5) and over half of total bed-days were unnecessary (57.4%; 95% СІ 56.4 to 58.5). The highest levels of stay were observed in hospitals’ general medicine departments (64.6%; 95% СІ 63.0 to 66.3)compared with other departments included in the analysis.ConclusionThe proposed method is robust in assessing the appropriateness of hospitalisations and duration of inpatient stays. The quantified levels of unnecessary hospital care indicate the need for improving efficiency and quality of care and optimising the excessive hospital capacities in Ukraine.

ObjectiveRandomised controlled trials (RCT) are the gold standard to provide unbiased data. However, when patients have a treatment preference, randomisation may influence participation and outcomes (eg, external and internal validity). The aim of this study was to assess the influence of patients’ preference in RCTs by analysing partially randomised patient preference trials (RPPT); an RCT and preference cohort combined.DesignSystematic review and meta-analyses.Data sourcesMEDLINE, Embase, PsycINFO and the Cochrane Library.Eligibility criteria for selecting studiesRPPTs published between January 2005 and October 2018 reporting on allocation of patients to randomised and preference cohorts were included.Data extraction and synthesisTwo independent reviewers extracted data. The main outcomes were the difference in external validity (participation and baseline characteristics) and internal validity (lost to follow-up, crossover and the primary outcome) between the randomised and the preference cohort within each RPPT, compared in a meta-regression using a Wald test. Risk of bias was not assessed, as no quality assessment for RPPTs has yet been developed.ResultsIn total, 117 of 3734 identified articles met screening criteria and 44 were eligible (24 873 patients). The participation rate in RPPTs was >95% in 14 trials (range: 48%–100%) and the randomisation refusal rate was >50% in 26 trials (range: 19%–99%). Higher education, female, older age, race and prior experience with one treatment arm were characteristics of patients declining randomisation. The lost to follow-up and cross-over rate were significantly higher in the randomised cohort compared with the preference cohort. Following the meta-analysis, the reported primary outcomes were comparable between both cohorts of the RPPTs, mean difference 0.093 (95% CI −0.178 to 0.364, p=0.502).ConclusionsPatients’ preference led to a substantial proportion of a specific patient group refusing randomisation, while it did not influence the primary outcome within an RPPT. Therefore, RPPTs could increase external validity without compromising the internal validity compared with RCTs.PROSPERO registration numberCRD42019094438.

ObjectivesProstate cancer is the second most common cause of cancer-related death in males after lung cancer, imposing a significant burden on the healthcare system in Australia. We propose the use of autoregressive integrated moving average (ARIMA) models in conjunction with population forecasts to provide for robust annual projections of prostate cancer.DesignData on the incidence and mortality from prostate cancer was obtained from the Australian Institute of Health and Welfare. We formulated several ARIMA models with different autocorrelation terms and chose one which provided for an accurate fit of the data based on the mean absolute percentage error (MAPE). We also assessed the model for external validity. A similar process was used to model age-standardised incidence and mortality rate for prostate cancer in Australia during the same time period.ResultsThe annual number of prostate cancer cases diagnosed in Australia increased from 3606 in 1982 to 20 065 in 2012. There were two peaks observed around 1994 and 2009. Among the various models evaluated, we found that the model with an autoregressive term of 1 (coefficient=0.45, p=0.028) as well as differencing the series provided the best fit, with a MAPE of 5.2%. External validation showed a good MAPE of 5.8% as well. We project prostate cancer incident cases in 2022 to rise to 25 283 cases (95% CI: 23 233 to 27 333).ConclusionOur study has accurately characterised the trend of prostate cancer incidence and mortality in Australia, and this information will prove useful for resource planning and manpower allocation.

Objective Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. Design Systematic review and meta-analysis of randomised controlled trials (RCTs). Setting Primary care. Participants Adults (≥18 years) who were iron deficient but non-anaemic. Interventions Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. Comparators Placebo or active therapy. Results We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) −0.38; 95% CI −0.52 to −0.23; I 2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI −0.15 to 0.37; I 2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I 2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I 2 58%; 14 trials; 616 participants). Conclusion In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia. PROSPERO registration number CRD42014007085.

Objective To explore the methodologies employed in studies assessing transition of care interventions, with the aim of defining goals for the improvement of future studies. Design Systematic review of comparative studies assessing transition to adult care interventions for young people with chronic conditions. Data sources MEDLINE, EMBASE, ClinicalTrial.gov. Eligibility criteria for selecting studies 2 reviewers screened comparative studies with experimental and quasi-experimental designs, published or registered before July 2015. Eligible studies evaluate transition interventions at least in part after transfer to adult care of young people with chronic conditions with at least one outcome assessed quantitatively. Results 39 studies were reviewed, 26/39 (67%) published their final results and 13/39 (33%) were in progress. In 9 studies (9/39, 23%) comparisons were made between preintervention and postintervention in a single group. Randomised control groups were used in 9/39 (23%) studies. 2 (2/39, 5%) reported blinding strategies. Use of validated questionnaires was reported in 28% (11/39) of studies. In terms of reporting in published studies 15/26 (58%) did not report age at transfer, and 6/26 (23%) did not report the time of collection of each outcome. Conclusions Few evaluative studies exist and their level of methodological quality is variable. The complexity of interventions, multiplicity of outcomes, difficulty of blinding and the small groups of patients have consequences on concluding on the effectiveness of interventions. The evaluation of the transition interventions requires an appropriate and common methodology which will provide access to a better level of evidence. We identified areas for improvement in terms of randomisation, recruitment and external validity, blinding, measurement validity, standardised assessment and reporting. Improvements will increase our capacity to determine effective interventions for transition care.

Introduction Hypertension is a major risk factor for cardiovascular diseases. In adults, high sodium intake is associated with elevated blood pressure. In children, experimental studies have shown that reducing sodium intake can reduce blood pressure. However, their external validity is limited, notably because the sodium reduction was substantial and not applicable in a real-life setting. Observational studies, on the other hand, allow assess the association between blood pressure and sodium intake across usual levels of consumption. There is also evidence that the association differs between subgroups of children according to age and body weight. Our objective is to conduct a systematic review and meta-analysis of experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents and to assess whether the association differs according to age and body weight. Methods and analysis A systematic search of the MEDLINE, EMBASE, CINAHL and CENTRAL databases will be conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age will be included. The exposure will be dietary sodium intake, estimated using different methods including urinary sodium excretion. The outcomes will be systolic and diastolic blood pressure, elevated blood pressure and hypertension. If appropriate, meta-analyses will be performed by pooling data across all studies together and separately for experimental and observational studies. Subgroup meta-analyses by age and body weight will be also conducted. Moreover, separate meta-analyses for different sodium intake levels will be conducted to investigate the dose–response relationship. Ethics and dissemination This systematic review and meta-analysis will be published in a peer-reviewed journal. A report will be prepared for national authorities and other stakeholders in the domains of nutrition, public health, and child health in Switzerland. Trial registration number CRD42016038245.

Objective Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses. Methods We screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches. Results We screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive. Conclusions We found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%).

Introduction The Disease Control Priorities Project recommends emergency care training for laypersons in low-resource settings, but evidence for these interventions has not yet been systematically reviewed. This review will identify the individual and community health effects of educating laypeople to deliver prehospital emergency care interventions in low-resource settings. Methods and analysis This systematic review addresses the following question: in underserviced populations and low-resource settings (P), does first aid or emergency care training or education for laypeople (I) confer any individual or community health benefit for emergency health conditions (O), in comparison with no training or other forms of education (C)? We restrict this review to studies reporting quantitatively measurable outcomes, and search 12 electronic bibliographic databases and grey literature sources. A team of expert content and methodology reviewers will conduct title and abstract screening and full-text review, using a custom-built online platform. Two investigators will independently extract methodological variables and outcomes related to patient-level morbidity and mortality and community-level effects on resilience or emergency care capacity. Two investigators will independently assess external validity, selection bias, performance bias, measurement bias, attrition bias and confounding. We will summarise the findings using a narrative approach to highlight similarities and differences between the gathered studies. Ethics and dissemination Formal ethical approval is not required. Results The results will be disseminated through a peer-reviewed publication and knowledge translation strategy. Review registration number CRD42014009685.

Objectives To first, validate in English hospitals the internal structure of the ‘Patient Evaluation of Emotional Care during Hospitalisation’ (PEECH) survey tool which was developed in Australia and, second, to examine how it may deepen the understanding of patient experience through comparison with results from the Picker Patient Experience Questionnaire (PPE-15). Design A 48-item survey questionnaire comprising both PEECH and PPE-15 was fielded. We performed exploratory factor analysis and then confirmatory factor analysis using a number of established fit indices. The external validity of the PEECH factor scores was compared across four participating services and at the patient level, factor scores were correlated with the PPE-15. Setting Four hospital services (an Emergency Admissions Unit; a maternity service; a Medicine for the Elderly department and a Haemato-oncology service) that contrasted in terms of the reported patient experience performance. Participants Selection of these acute service settings was based on achieving variation of the following factors: teaching hospital/district general hospital, urban/rural locality and high-performing/low-performing organisations (using results of annual national staff and patient surveys). A total of 423 surveys were completed by patients (26% response rate). Results A different internal structure to the PEECH instrument emerged in English hospitals. However, both the existing and new factor models were similar in terms of fit. The correlations between the new PEECH factors and the PPE-15 were all in the expected direction, but two of the new factors (personal interactions and feeling valued) were more strongly associated with the PPE-15 than the remaining two factors (feeling informed and treated as an individual). Conclusions PEECH can help to build an understanding of complex interpersonal aspects of quality of care, alongside the more transactional and functional aspects typically captured by PPE-15. Further testing of the combined instrument should be undertaken in a wider range of healthcare settings.

ObjectiveTo evaluate the clinical efficacy and effectiveness of using 3D printing to develop medical devices across all medical fields.DesignSystematic review compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Data sourcesPubMed, Web of Science, OVID, IEEE Xplore and Google Scholar.MethodsA double-blinded review method was used to select all abstracts up to January 2017 that reported on clinical trials of a three-dimensional (3D)-printed medical device. The studies were ranked according to their level of evidence, divided into medical fields based on the International Classification of Diseases chapter divisions and categorised into whether they were used for preoperative planning, aiding surgery or therapy. The Downs and Black Quality Index critical appraisal tool was used to assess the quality of reporting, external validity, risk of bias, risk of confounding and power of each study.ResultsOf the 3084 abstracts screened, 350 studies met the inclusion criteria. Oral and maxillofacial surgery contained 58.3% of studies, and 23.7% covered the musculoskeletal system. Only 21 studies were randomised controlled trials (RCTs), and all fitted within these two fields. The majority of RCTs were 3D-printed anatomical models for preoperative planning and guides for aiding surgery. The main benefits of these devices were decreased surgical operation times and increased surgical accuracy.ConclusionsAll medical fields that assessed 3D-printed devices concluded that they were clinically effective. The fields that most rigorously assessed 3D-printed devices were oral and maxillofacial surgery and the musculoskeletal system, both of which concluded that the 3D-printed devices outperformed their conventional comparators. However, the efficacy and effectiveness of 3D-printed devices remain undetermined for the majority of medical fields. 3D-printed devices can play an important role in healthcare, but more rigorous and long-term assessments are needed to determine if 3D-printed devices are clinically relevant before they become part of standard clinical practice.

ObjectiveTo explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients.Study design and settingUsing individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV).ResultsPrior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions.ConclusionsPredictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully.Trial registration numberPROSPERO id: CRD42018088129.

IntroductionIn order for study results to be relevant for practice, the study participants should represent the source population. A common problem is recruitment of sufficient and representative subjects, threatening the external validity of the study and, ultimately, evidence-based practice. The aim was to highlight common challenges and to present possible solutions to recruitment.MethodsUsing four recent randomised controlled trials as examples, common recruitment challenges were highlighted and solutions were proposed. The four studies represented some common and some specific challenges, but they investigated interventions for the prevention of the two major public health challenges of today: musculoskeletal pain and common mental disorders.ResultsIdentified challenges and suggested solutions were presented as a checklist to be used for future trials in order to aid recruitment and reporting thereof.