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Key Points Question How is the COVID-19 pandemic associated with risks and benefits of standard cancer therapy? Findings In this comparative effectiveness study reanalyzing data from 8 randomized trials across oncology, radiation fractionation was not associated with outcomes in low COVID-19–risk scenarios. In higher-risk scenarios, aggressive hypofractionation was associated with a survival benefit, whereas moderate hypofractionation was not. Meaning These findings suggest that the expected benefit of altering radiation therapy during the COVID-19 pandemic is associated with local pandemic factors and the specifics of treatment modification, and can be estimated using a quantitative framework based on completed randomized trials to support treatment decision-making., This comparative effectiveness study investigates how the COVID-19 pandemic is associated with the benefits and risks of standard radiation therapy in simulated patients., Importance During the COVID-19 pandemic, cancer therapy may put patients at risk of SARS-CoV-2 infection and mortality. The impacts of proposed alternatives on reducing infection risk are unknown. Objective To investigate how the COVID-19 pandemic is associated with the risks and benefits of standard radiation therapy (RT). Design, Setting, and Participants This comparative effectiveness study used estimated individual patient–level data extracted from published Kaplan-Meier survival figures from 8 randomized clinical trials across oncology from 1993 to 2014 that evaluated the inclusion of RT or compared different RT fractionation regimens. Included trials were Dutch TME and TROG 01.04 examining rectal cancer; CALGB 9343, OCOG hypofractionation trial, FAST-Forward, and NSABP B-39 examining early stage breast cancer, and CHHiP and HYPO-RT-PC examining prostate cancer. Risk of SARS-CoV-2 infection and mortality associated with receipt of RT in the treatment arms were simulated and trials were reanalyzed. Data were analyzed between April 1, 2020, and June 30, 2020. Exposures COVID-19 risk associated with treatment was simulated across different pandemic scenarios, varying infection risk per fractions (IRFs) and case fatality rates (CFRs). Main Outcomes and Measures Overall survival was evaluated using Cox proportional hazards modeling under different pandemic scenarios. Results Estimated IPLD from a total of 14 170 patients were included in the simulations. In scenarios with low COVID-19-associated risks (IRF, 0.5%; CFR, 5%), fractionation was not significantly associated with outcomes. In locally advanced rectal cancer, short-course RT was associated with better outcomes than long-course chemoradiation (TROG 01.04) and was associated with similar outcomes as RT omission (Dutch TME) in most settings (eg, TROG 01.04 median HR, 0.66 [95% CI, 0.46-0.96]; Dutch TME median HR, 0.91 [95% CI, 0.80-1.03] in a scenario with IRF 5% and CFR 20%). Moderate hypofractionation in early stage breast cancer (OCOG hypofractionation trial) and prostate cancer (CHHiP) was not associated with survival benefits in the setting of COVID-19 (eg, OCOG hypofractionation trial median HR, 0.89 [95% CI, 0.74-1.06]; CHHiP median HR, 0.87 [95% CI, 0.75-1.01] under high-risk scenario with IRF 10% and CFR 30%). More aggressive hypofractionation (FAST-Forward, HYPO-RT-PC) and accelerated partial breast irradiation (NSABP B-39) were associated with improved survival in higher risk scenarios (eg, FAST-Forward median HR, 0.58 [95% CI, 0.49-0.68]; HYPO-RT-PC median HR, 0.60 [95% CI, 0.48-0.75] under scenario with IRF 10% and CFR 30%). Conclusions and Relevance In this comparative effectiveness study of data from 8 clinical trials of patients receiving radiation therapy to simulate COVID-19 risk and mortality rates, treatment modification was not associated with altered risk from COVID-19 in lower-risk scenarios and was only associated with decreased mortality in very high COVID-19–risk scenarios. This model, which can be adapted to dynamic changes in COVID-19 risk, provides a flexible, quantitative approach to assess the potential impact of treatment modifications and supports the continued delivery of standard evidence-based care with appropriate precautions against COVID-19.

ObjectiveTo investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care.DesignCluster randomised controlled trial.Setting47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018.ParticipantsIn each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years.InterventionsOpportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks.Main outcome measuresDifference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices.ResultsFollow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found.ConclusionsOpportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting.Trial registrationNetherlands Trial Register No NL4776 (old NTR4914).

Key Points Question Can machine learning models predict improvement of various depressive symptoms with antidepressant treatment based on pretreatment symptom scores and electroencephalographic measures? Findings In this prognostic study, using the machine learning approach of gradient-boosted decision trees, the ElecTreeScore algorithm could reliably distinguish the patients who responded to treatment from those who did not based on various depressive symptoms using pretreatment symptom scores and electroencephalographic features (using the cross-validation approach on 518 patients). Meaning Machine learning approaches that include pretreatment symptom scores and electroencephalographic features may help predict which depressive symptoms will improve with antidepressants., Importance Despite the high prevalence and potential outcomes of major depressive disorder, whether and how patients will respond to antidepressant medications is not easily predicted. Objective To identify the extent to which a machine learning approach, using gradient-boosted decision trees, can predict acute improvement for individual depressive symptoms with antidepressants based on pretreatment symptom scores and electroencephalographic (EEG) measures. Design, Setting, and Participants This prognostic study analyzed data collected as part of the International Study to Predict Optimized Treatment in Depression, a randomized, prospective open-label trial to identify clinically useful predictors and moderators of response to commonly used first-line antidepressant medications. Data collection was conducted at 20 sites spanning 5 countries and including 518 adult outpatients (18-65 years of age) from primary care or specialty care practices who received a diagnosis of current major depressive disorder between December 1, 2008, and September 30, 2013. Patients were antidepressant medication naive or willing to undergo a 1-week washout period of any nonprotocol antidepressant medication. Statistical analysis was conducted from January 5 to June 30, 2019. Exposures Participants with major depressive disorder were randomized in a 1:1:1 ratio to undergo 8 weeks of treatment with escitalopram oxalate (n = 162), sertraline hydrochloride (n = 176), or extended-release venlafaxine hydrochloride (n = 180). Main Outcomes and Measures The primary objective was to predict improvement in individual symptoms, defined as the difference in score for each of the symptoms on the 21-item Hamilton Rating Scale for Depression from baseline to week 8, evaluated using the C index. Results The resulting data set contained 518 patients (274 women; mean [SD] age, 39.0 [12.6] years; mean [SD] 21-item Hamilton Rating Scale for Depression score improvement, 13.0 [7.0]). With the use of 5-fold cross-validation for evaluation, the machine learning model achieved C index scores of 0.8 or higher on 12 of 21 clinician-rated symptoms, with the highest C index score of 0.963 (95% CI, 0.939-1.000) for loss of insight. The importance of any single EEG feature was higher than 5% for prediction of 7 symptoms, with the most important EEG features being the absolute delta band power at the occipital electrode sites (O1, 18.8%; Oz, 6.7%) for loss of insight. Over and above the use of baseline symptom scores alone, the use of both EEG and baseline symptom features was associated with a significant increase in the C index for improvement in 4 symptoms: loss of insight (C index increase, 0.012 [95% CI, 0.001-0.020]), energy loss (C index increase, 0.035 [95% CI, 0.011-0.059]), appetite changes (C index increase, 0.017 [95% CI, 0.003-0.030]), and psychomotor retardation (C index increase, 0.020 [95% CI, 0.008-0.032]). Conclusions and Relevance This study suggests that machine learning may be used to identify independent associations of symptoms and EEG features to predict antidepressant-associated improvements in specific symptoms of depression. The approach should next be prospectively validated in clinical trials and settings. Trial Registration ClinicalTrials.gov Identifier: NCT00693849, This prognostic study examines the extent to which a machine learning approach, using gradient-boosted decision trees, can predict acute improvement in individual depressive symptoms with antidepressants based on pretreatment symptom scores and electroencephalographic measures.

Background There is an agreement that the methodological quality of randomized trials should be assessed in systematic reviews, but there is a debate on how this should be done. We conducted a construct validation study of the Physiotherapy Evidence Database (PEDro) scale, which is widely used to assess the quality of trials in physical therapy and rehabilitation. Methods We analyzed 345 trials that were included in Cochrane reviews and for which a PEDro summary score was available. We used one- and two-parameter logistic item response theory (IRT) models to study the psychometric properties of the PEDro scale and assessed the items' difficulty and discrimination parameters. We ran goodness of fit post estimations and examined the IRT unidimensionality assumption with a multidimensional IRT (MIRT) model. Results Out of a maximum of 10, the mean PEDro summary score was 5.46 (SD = 1.51). The allocation concealment and intention-to-treat scale items contributed most of the information on the underlying construct (with discriminations of 1.79 and 2.05, respectively) at similar difficulties (0.63 and 0.65, respectively). The other items provided little additional information and did not distinguish trials of different quality. There was substantial evidence of departure from the unidimensionality assumption, suggesting that the PEDro items relate to more than one latent trait. Conclusions Our findings question the construct validity of the PEDro scale to assess the methodological quality of clinical trials. PEDro summary scores should not be used; rather, the physiotherapy community should consider working with the individual items of the scale.

Background: Blood glucose control in the intensive care unit (ICU) has the potential to save lives. However, maintaining blood glucose concentrations within a chosen target range is difficult in clinical practice and holds risk of potentially harmful hypoglycemia. Clinically validated computer algorithms to guide insulin dosing by nurses have been advocated for better and safer blood glucose control. Methods: We conducted an international, multicenter, randomized controlled trial involving 1550 adult, medical and surgical critically ill patients, requiring blood glucose control. Patients were randomly assigned to algorithm-guided blood glucose control (LOGIC-C, n = 777) or blood glucose control by trained nurses (Nurse-C, n = 773) during ICU stay, according to the local target range (80-110 mg/dL or 90-145 mg/dL). The primary outcome measure was the quality of blood glucose control, assessed by the glycemic penalty index (GPI), a measure that penalizes hypoglycemic and hyperglycemic deviations from the chosen target range. Incidence of severe hypoglycemia (

Key Points Question Is alcohol consumption associated with the risk of dementia and cognitive decline in older adults with or without mild cognitive impairment? Findings In this cohort study of 3021 participants aged 72 years and older, alcohol intake within recommended limits was not significantly associated with a lower risk of dementia among participants with or without mild cognitive impairment at baseline. Among participants without mild cognitive impairment, daily low-quantity drinking was associated with lower dementia risk compared with infrequent higher-quantity drinking. Meaning These findings suggest that physicians caring for older adults need to carefully assess the full dimensions of drinking behavior and cognition when providing guidance to patients about their alcohol consumption., This cohort study examines the association between alcohol intake and risk of dementia among older adults with or without mild cognitive impairment., Importance Substantial heterogeneity and uncertainty exist in the observed associations between alcohol consumption and dementia. Objective To assess the association between alcohol consumption and dementia and the roles of mild cognitive impairment (MCI) and apolipoprotein E ε4 (APOE E4) genotype in modifying this association. Design, Setting, and Participants This cohort study used data from the Ginkgo Evaluation of Memory Study, conducted from 2000 to 2008 among US community-dwelling participants. This study analyzed 3021 participants aged 72 years and older who were free of dementia. Data analysis was performed from 2017 to 2018. Exposures Self-reported alcohol consumption, drinking frequency, and quantity. Main Outcomes and Measures Using multivariable proportional hazards regression and linear mixed models, the risk of dementia and the rate of change over time in the Modified Mini-Mental State Examination were estimated. Results Among 3021 participants, the median (interquartile range) age was 78 (76-80) years; 1395 (46.2%) were female. During a median (interquartile range) follow-up of 6.0 (4.9-6.5) years, 512 cases of dementia occurred. For 7.1 to 14.0 drinks per week compared with less than 1.0 drink per week, the hazard ratios for dementia were 0.63 (95% CI, 0.38-1.06) among 2548 participants without MCI and 0.93 (95% CI, 0.47-1.84) among 473 participants with MCI. Among participants with MCI, the hazard ratio for dementia was 1.72 (95% CI, 0.87-3.40) for more than 14.0 drinks per week compared with less than 1.0 drink per week. The association of alcohol intake with dementia differed for participants with and without baseline MCI (P for interaction = .03). Among participants without MCI, daily low-quantity drinking was associated with lower dementia risk than infrequent higher-quantity drinking (hazard ratio, 0.45; 95% CI, 0.23-0.89; P = .02). Findings were consistent when stratified by sex, age, and APOE E4 genotype. Compared with drinking less than 1.0 drink per week, complete abstention (in participants without MCI) and the consumption of more than 14.0 drinks per week (in participants with MCI) were associated with lower Modified Mini-Mental State Examination scores (mean difference at follow-up compared with baseline, −0.46 point [95% CI, −0.87 to −0.04 point] and −3.51 points [95% CI, −5.75 to −1.27 points], respectively). Conclusions and Relevance In this study, complete abstention and consuming more than 14.0 drinks per week (compared with drinking

Background/aims Use of electronic health records and information technology to deliver more efficient clinical trials is attracting the attention of research funders and researchers. We report on methodological issues and data quality for a comparison of ‘automated’ and manual (or ‘in-practice’) methods for recruitment and randomisation in a large randomised controlled trial, with individual patient allocation in primary care. Methods We conducted a three-arm randomised controlled trial in primary care to evaluate interventions to improve the uptake of invited NHS health checks for cardiovascular risk assessment. Eligible participants were identified using a borough-wide health check management information system. An in-practice recruitment and randomisation method used at 12 general practices required the research team to complete monthly visits to each general practice. For the fully automated method, employed for six general practices, randomisation of eligible participants was performed automatically and remotely using a bespoke algorithm embedded in the health check management information system. Results There were 8588 and 4093 participants recruited for the manual and automated methods, respectively. The in-practice method was ready for implementation 3 months sooner than the automated method and the in-practice method allowed for full control and documentation of the randomisation procedure. However the in-practice approach was labour intensive and the requirement for participant records to be stored locally resulted in the loss of data for 10 practice months. No records for participants allocated using the automated method were lost. A fixed-effects meta-analysis showed that effect estimates for the primary outcome were consistent for the two allocation methods. Conclusions This trial demonstrated the feasibility of automated recruitment and randomisation methods into a randomised controlled trial performed in primary care. Future research should explore the application of these techniques in other clinical contexts and health care settings. Trial registration Current Controlled Trials, ID: ISRCTN42856343. Registered on 21 March 2013 Electronic supplementary material The online version of this article (10.1186/s13063-018-2723-3) contains supplementary material, which is available to authorized users.

Background SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims:To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial.To support the trial’s clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. Methods A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre’s equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. Results 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8–67.8cm3; and PTV volumes 221.9–513.3 cm3. For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial. Conclusions The SCOPE 1 QA programme outcomes lend support to the trial’s clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol. Trial registration The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479. Electronic supplementary material The online version of this article (10.1186/s13014-017-0916-7) contains supplementary material, which is available to authorized users.

Objectives: To investigate the cost-effectiveness of a telehealth intervention for primary care patients with raised cardiovascular disease (CVD) risk.Design: A prospective within-trial patient-level economic evaluation conducted alongside a randomised controlled trial.Setting: Patients recruited through primary care, and intervention delivered via telehealth service. Participants: Adults with a 10-year CVD risk ≥20%, as measured by the QRISK2 algorithm, with at least one modifiable risk factor. Intervention: A series of up to 13 scripted, theory-led telehealth encounters with healthcare advisors, who supported participants to make behaviour change, use online resources, optimise medication, and improve adherence. Participants in the control arm received usual care. Primary and secondary outcome measures: Cost-effectiveness measured by net monetary benefit at the end of 12 months of follow-up, calculated from incremental cost and incremental quality-adjusted life years (QALYs). Productivity impacts, participant out-of-pocket expenditure, and the clinical outcome were presented in a cost-consequences framework.Results: 641 participants were randomised – 325 to receive the telehealth intervention in addition to usual care and 316 to receive only usual care. 18% of participants had missing data on either costs, utilities, or both. Multiple imputation was used for the base case results. The intervention was associated with incremental mean per-patient NHS costs of £138 (95% CI: £66 to £211) and an incremental QALY gain of 0.012 (95% CI:-0.001 to 0.026). The incremental cost-effectiveness ratio was £10,859. Net monetary benefit at a cost-effectiveness threshold of £20,000 per QALY was £116 (95% CI: -£58 to £291), and the probability that the intervention was cost-effective at this threshold value was 0.77. Similar results were obtained from a complete-case analysis.Conclusions: There is evidence to suggest that the Healthlines telehealth intervention was likely to be cost-effective at a threshold of £20,000 per QALY.Trial registration: ISRCTN27508731, prospectively registered 05/07/2012

The OPTI-SCRIPT cluster randomised controlled trial (RCT) found that a three-phase multifaceted intervention including academic detailing with a pharmacist, GP-led medicines reviews, supported by web-based pharmaceutical treatment algorithms, and tailored patient information leaflets, was effective in reducing potentially inappropriate prescribing (PIP) in Irish primary care. We report a process evaluation exploring the implementation of the intervention, the experiences of those participating in the study and lessons for future implementation. The OPTI-SCRIPT trial included 21 GP practices and 196 patients. The process evaluation used mixed methods. Quantitative data were collected from all GP practices and semi-structured interviews were conducted with GPs from intervention and control groups, and a purposive sample of patients from the intervention group. All interviews were transcribed verbatim and analysed using a thematic analysis. Despite receiving a standardised academic detailing session, intervention delivery varied among GP practices. Just over 70 % of practices completed medicines review as recommended with the patient present. Only single-handed practices conducted reviews without patients present, highlighting the influence of practice characteristics and resources on variation. Medications were more likely to be completely stopped or switched to another more appropriate medication when reviews were conducted with patients present. The patient information leaflets were not used by any of the intervention practices. Both GP (32 %) and patient (40 %) recruitment rates were modest. For those who did participate, overall, the experience was positively viewed, with GPs and patients referring to the value of medication reviews to improve prescribing and reduce unnecessary medications. Lack of time in busy GP practices and remuneration were identified as organisational barriers to future implementation. The OPTI-SCRIPT intervention was positively viewed by both GPs and patients, both of whom valued the study’s objectives. Patient information leaflets were not a successful component of the intervention. Academic detailing and medication reviews are important components in changing PIP, and having patients present during the review process seems to be a more effective approach for decreasing PIP. Current controlled trials ISRCTN41694007 . Registered on 21 March 2012.

Background Acute kidney injury is a common complication after major surgery. In this study, we investigated whether an algorithm-guided goal-directed haemodynamic therapy (GDT) can improve renal outcome compared to good standard clinical care. Methods A total of 180 patients undergoing major abdominal surgery were prospectively and randomly assigned to one of two groups: in the GDT group, patients were treated with a GDT algorithm using transpulmonary thermodilution while standard care was applied to the control patients. Change in creatinine was studied as the primary end point, postoperative complications as well as 1-year mortality as secondary outcomes. Haemodynamics in GDT and control patients were compared calculating goal-achievement rates. Results Postoperative change in creatinine (18 ± 39 μmol/l (control) vs. 16 ± 42 μmol/l (GDT); mean difference (95 % confidence interval) 1.6 μmol/l (−10 to 13 μmol/l)) was comparable between the GDT and the control group. Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm. Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high (>80 %) rates in the control group. Multivariate regression analysis revealed intraoperative hypotension (MAP 2) as risk factors for postoperative renal impairment. Conclusions In this study, GDT was not superior to standard clinical care in order to avoid renal failure after major abdominal surgery. The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group, which cannot be improved by the GDT algorithm. Trial registration Clinicaltrials.gov; NCT01035541; registered 17 December 2009.

Background On South African public hospital wards, observation charts do not incorporate early warning scoring (EWS) systems to inform nurses when to summon assistance. The aim of this trial was to test the impact of a new chart incorporating a modified EWS (MEWS) system and a linked training program on nurses’ responses to clinical deterioration (primary outcome). Secondary outcomes were: numbers of patients with vital signs recordings in the first eight postoperative hours; number of times each vital sign was recorded; and nurses’ knowledge. Methods/design A pragmatic, parallel-group, cluster randomized, controlled clinical trial of intervention versus standard care was conducted in three intervention and three control adult surgical wards in an 867-bed public hospital in Cape Town, between March and July 2010; thereafter the MEWS chart was withdrawn. A total of 50 out of 122 nurses in full-time employment participated. From 1,427 case notes, 114 were selected by randomization for assessment. The MEWS chart was implemented in intervention wards. Control wards delivered standard care, without training. Case notes were reviewed two weeks after the trial’s completion. Knowledge was assessed in both trial arms by blinded independent marking of written tests before and after training of nurses in intervention wards. Analyses were undertaken with IBM SPSS software on an intention-to-treat basis. Results Patients in trial arms were similar. Introduction of the MEWS was not associated with statistically significant changes in responses to clinical deterioration (50 of 57 received no assistance versus 55 of 57, odds ratio (OR): 0.26, 95% confidence interval (CI): 0.05 to 1.31), despite improvement in nurses’ knowledge in intervention wards. More patients in intervention than control wards had recordings of respiratory rate (27 of 57 versus 2 of 57, OR: 24.75, 95% CI: 5.5 to 111.3) and recordings of all seven parameters (5 of 57 versus 0 of 57 patients, risk estimate: 1.10, 95% CI: 1.01 to 1.2). Conclusions A MEWS chart and training program enhanced recording of respiratory rate and of all parameters, and nurses’ knowledge, but not nurses’ responses to patients who triggered the MEWS reporting algorithm. Trial registration This trial was registered with the Pan African Clinical Trials Registry (identifier: PACTR201309000626545) on 9 September 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0624-2) contains supplementary material, which is available to authorized users.

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk=-365 cases/year, sham minus active; 95% confidence interval (CI) , -2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches. Key words: drinking water, gastrointestinal, intervention trial, microbial risk assessment, waterborne pathogens.

Background: In spite of national guidelines which do not recommend prostate specific antigen (PSA) screening for prostate cancer or are inconclusive, Canadian men may be accessing the screening test. Methods: For the purpose of informing prostate screening policy, cross-sectional self-reported data from the Canadian Community Health Survey (2000–2001) were analyzed to determine the lifetime and recent PSA screening prevalence of Canadian men aged 50 and older with no prostate cancer, and to explore the socio-demographic characteristics associated with ever being screened. Multivariate binomial regression analyses were used to calculate prevalence rate ratios as a measure of association between respondents’ characteristics and PSA screening behaviour. Results: Almost half of Canadian men over the age of 50 years (47.5%; 95% CI=46.4–48.5) reported receiving PSA screening during their lifetime. Seventy-two percent (71.8%) of PSA screening was performed within one year prior to the survey or recently. Lifetime prevalence was highest among men aged 60–69 (53.1%; 95% CI=51.1–55.1). Next to advanced age, having a family doctor was the most predictive of screening behaviour (PRR=1.83, p≤0.01). Black ethnicity, a risk factor for prostate cancer, failed to be predictive of screening (PRR=1.04, NS). Not speaking French or English was strongly associated with not obtaining a PSA screen (PRR=0.66, p≤0.01). Interpretation: Our finding that Canadian men commonly reported PSA screening for prostate cancer is not congruent with national guidelines. While we wait for randomized controlled trial evidence of the effectiveness of PSA screening in reducing mortality due to prostate cancer, PSA screening has emerged as a public health issue.

Background Internet-based self-management has shown to improve asthma control and asthma related quality of life, but the improvements were only marginally clinically relevant for the group as a whole. We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma. Methods In a 1-year randomised controlled trial involving 200 adults (18-50 years) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Questionnaire (ACQ). Participants were assigned either to the Internet group (n = 101) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group (UC) (n = 99). We analysed 3 subgroups: patients with well controlled (ACQ ≤ 0.75), partly controlled (0.75>ACQ ≤ 1.5) or uncontrolled (ACQ>1.5) asthma at baseline. Results Overall monitoring adherence was 67% (95% CI, 60% to 74%). Improvements in ACQ score after 12 months were -0.14 (p = 0.23), -0.52 (p < 0.001) and -0.82 (p < 0.001) in the Internet group compared to usual care for patients with well, partly and uncontrolled asthma at baseline, respectively. Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma (+278 μg, p = 0.001), but not in patients with well or partly controlled asthma. After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care. Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients' needs. Trial registration Current Controlled Trials ISRCTN79864465

OBJECTIVE: To evaluate a simple cardiovascular risk management package for assessing and managing cardiovascular risk using hypertension as an entry point in primary care facilities in low-resource settings. METHODS: Two geographically distant regions in two countries (China and Nigeria) were selected and 10 pairs of primary care facilities in each region were randomly selected and matched. Regions were then randomly assigned to a control group, which received usual care, or to an intervention group, which applied the cardiovascular risk management package. Each facility enrolled 60 consecutive patients with hypertension. Intervention sites educated patients about risk factors at baseline and initiated treatment with hydrochlorothiazide at 4 months in patients at medium risk of a cardiovascular event, according to a standardized treatment algorithm. Systolic blood pressure change from baseline to 12 months was the primary outcome measure. FINDINGS: The study included 2397 patients with baseline hypertension: 1191 in 20 intervention facilities and 1206 in 20 control facilities. Systolic and diastolic blood pressure decreased more in intervention patients than in controls. However, at 12 months more than half of patients still had uncontrolled hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg). Behavioural risk factors had improved among intervention patients in Nigeria but not in China. Only about 2% of hypertensive patients required referral to the next level of care. CONCLUSION: Even in low-resource settings, hypertensive patients can be effectively assessed and managed in primary care facilities.

Objective To compare the effectiveness of an algorithm for diagnosis of active labour in primiparous women with standard care in terms of maternal and neonatal outcomes. Design Cluster randomised trial. Setting Maternity units in Scotland with at least 800 annual births. Participants 4503 women giving birth for the first time, in 14 maternity units. Seven experimental clusters collected data from a baseline sample of 1029 women and a post-implementation sample of 896 women. The seven control clusters had a baseline sample of 1291 women and a post-implementation sample of 1287 women. Intervention Use of an algorithm by midwives to assist their diagnosis of active labour, compared with standard care. Main outcomes Primary outcome: use of oxytocin for augmentation of labour. Secondary outcomes: medical interventions in labour, admission management, and birth outcome. Results No significant difference was found between groups in percentage use of oxytocin for augmentation of labour (experimental minus control, difference=0.3, 95% confidence interval −9.2 to 9.8; P=0.9) or in the use of medical interventions in labour. Women in the algorithm group were more likely to be discharged from the labour suite after their first labour assessment (difference=−19.2, −29.9 to −8.6; P=0.002) and to have more pre-labour admissions (0.29, 0.04 to 0.55; P=0.03). Conclusions Use of an algorithm to assist midwives with the diagnosis of active labour in primiparous women did not result in a reduction in oxytocin use or in medical intervention in spontaneous labour. Significantly more women in the experimental group were discharged home after their first labour ward assessment. Trial registration Current Controlled Trials ISRCTN00522952.

First Nations people with diabetes mellitus and hypertension are at greater risk of renal and cardiovascular complications than are non-native patients because of barriers to health care services. We conducted this randomized controlled trial to assess whether a community-based treatment strategy implemented by home care nurses would be effective in controlling hypertension in First Nations people with existing hypertension and type 2 diabetes.We compared 2 community-based strategies for controlling hypertension in First Nations people with existing hypertension and diabetes. In the intervention group, a home care nurse followed a predefined treatment algorithm of pharmacologic antihypertensive therapy. In the control group, treatment decisions were made by each subject's primary care physician. The primary outcome measure was the difference between the 2 groups in the change in systolic blood pressure after 12 months. Secondary outcome measures were the change in diastolic blood pressure over time, the change in urine albumin status and the incidence of adverse events.Both groups experienced a significant reduction in systolic blood pressure by the final visit (by 24.0 [standard deviation (SD) 13.5] mm Hg in the intervention group and by 17.0 [SD 18.6] mm Hg in the control group); p0.001 in each case). However, the difference between the 2 groups in this change was not significant. Patients in the intervention group had a larger decrease in diastolic blood pressure over time than did those in the control group (by 11.6 [SD 10.6] mm Hg v. 6.8 [SD 11.1] mm Hg respectively; p = 0.05). The groups did not differ significantly in terms of changes in urine albumin excretion or incidence of adverse events.High rates of blood pressure control in the community were achieved in both groups in the DREAM 3 study. The addition of a home care nurse to implement a treatment strategy for blood pressure control was more effective in lowering diastolic than systolic blood pressure compared with home care visits for blood pressure monitoring alone and follow-up treatment by a family physician.

Objectives To assess whether adding a novel computerised diagnostic tool, the MoleMate system (SIAscopy with primary care scoring algorithm), to current best practice results in more appropriate referrals of suspicious pigmented lesions to secondary care, and to assess its impact on clinicians and patients. Design Randomised controlled trial. Setting 15 general practices in eastern England. Participants 1297 adults with pigmented skin lesions not immediately diagnosed as benign. Interventions Patients were assessed by trained primary care clinicians using best practice (clinical history, naked eye examination, seven point checklist) either alone (control group) or with the MoleMate system (intervention group). Main outcome measures Appropriateness of referral, defined as the proportion of referred lesions that were biopsied or monitored. Secondary outcomes related to the clinicians (diagnostic performance, confidence, learning effects) and patients (satisfaction, anxiety). Economic evaluation, diagnostic performance of the seven point checklist, and five year follow-up of melanoma incidence were also secondary outcomes and will be reported later. Results 1297 participants with 1580 lesions were randomised: 643 participants with 788 lesions to the intervention group and 654 participants with 792 lesions to the control group. The appropriateness of referral did not differ significantly between the intervention or control groups: 56.8% (130/229) v 64.5% (111/172); difference −8.1% (95% confidence interval −18.0% to 1.8%). The proportion of benign lesions appropriately managed in primary care did not differ (intervention 99.6% v control 99.2%, P=0.46), neither did the percentage agreement with an expert decision to biopsy or monitor (intervention 98.5% v control 95.7%, P=0.26). The percentage agreement with expert assessment that the lesion was benign was significantly lower with MoleMate (intervention 84.4% v control 90.6%, P

Background A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase. Methods Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery. Results A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups. Conclusion Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.

Introduction Daily interruption of sedation (DIS) and sedation algorithms (SAs) have been shown to decrease mechanical ventilation (MV) duration. We conducted a randomized study comparing these strategies. Methods Mechanically ventilated adults 18 years old or older in the medical intensive care unit (ICU) were randomly assigned to DIS or SA. Exclusion criteria were severe neurocognitive dysfunction, administration of neuromuscular blockers, and tracheostomy. Study endpoints were total MV duration and 28-day ventilator-free survival. Results The study was terminated prematurely after 74 patients were enrolled (DIS 36 and SA 38). The two groups had similar age, gender, racial distribution, Acute Physiology and Chronic Health Evaluation II score, and reason for MV. The Data Safety Monitoring Board convened after DIS patients were found to have higher hospital mortality; however, no causal connection between DIS and increased mortality was identified. Interim analysis demonstrated a significant difference in primary endpoint, and study termination was recommended. The DIS group had longer total duration of MV (median 6.7 versus 3.9 days; P = 0.0003), slower improvement of Sequential Organ Failure Assessment over time (0.70 versus 0.23 units per day; P = 0.025), longer ICU length of stay (15 versus 8 days; P < 0.0001), and longer hospital length of stay (23 versus 12 days; P = 0.01). Conclusion In our cohort of patients, the use of SA was associated with reduced duration of MV and lengths of stay compared with DIS. Based on these results, DIS may not be appropriate in all mechanically ventilated patients. Trial registration ClinicalTrials.gov NCT00205517.

Virtual reality (VR)-based rehabilitation has been reported to have beneficial effects on upper extremity function in stroke survivors; however, there is limited information about its effects on distal upper extremity function and health-related quality of life (HRQoL). The purpose of the present study was to examine the effects of VR-based rehabilitation combined with standard occupational therapy on distal upper extremity function and HRQoL, and compare the findings to those of amount-matched conventional rehabilitation in stroke survivors. The present study was a single-blinded, randomized controlled trial. The study included 46 stroke survivors who were randomized to a Smart Glove (SG) group or a conventional intervention (CON) group. In both groups, the interventions were targeted to the distal upper extremity and standard occupational therapy was administered. The primary outcome was the change in the Fugl–Meyer assessment (FM) scores, and the secondary outcomes were the changes in the Jebsen–Taylor hand function test (JTT), Purdue pegboard test, and Stroke Impact Scale (SIS) version 3.0 scores. The outcomes were assessed before the intervention, in the middle of the intervention, immediately after the intervention, and 1 month after the intervention. The improvements in the FM (FM-total, FM-prox, and FM-dist), JTT (JTT-total and JTT-gross), and SIS (composite and overall SIS, SIS-social participation, and SIS-mobility) scores were significantly greater in the SG group than in the CON group. VR-based rehabilitation combined with standard occupational therapy might be more effective than amount-matched conventional rehabilitation for improving distal upper extremity function and HRQoL. This study is registered under the title “Effects of Novel Game Rehabilitation System on Upper Extremity Function of Patients With Stroke” and can be located in https://clinicaltrials.gov with the study identifier NCT02029651 .

Introduction Nutrition is crucial to successful outcomes in peri-operative head and neck cancer patients. Nasogastric feeding tubes are an accepted and safe method of providing enteral nutrition in the short-term. Many methods have been advocated for successfully inserting and securing nasogastric tubes and each practitioner will have his or her preferred technique. Objectives To confirm the effectiveness of using gel caps combined with the flexible nasendoscope for the insertion of nasogastric feeding tubes in head and neck cancer patients following failure of traditional methods. Participants Thirty-five consecutive patients requiring nasogastric feeding tubes were included in this comparative audit. All had failed traditional insertion methods after 2 attempts and were therefore eligible for inclusion. Patients were randomised to undergo attempted insertion with the flexible nasendoscope with or without the use of a gel cap (both methods have been previously described). Audit Outcome Primary outcome measures showed no significant difference between the two techniques. Discussion We found the methodology to be of no greater benefit to our patients when compared to our alternative current practice for failed blind nasogastric tube insertion. We retain this methodology in our armamentarium for difficult circumstances but have continued with our standard practice for most patients needing nasogastric tube placement.