Protocol for a feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients

IntroductionOxygen is the most commonly administered drug to mechanically ventilated critically ill adults, yet little is known about the optimum oxygen saturation (SpO2) target for these patients; the current standard of care is an SpO2of 96% or above. Small pilot studies have demonstrated that permissive hypoxaemia (aiming for a lower SpO2than normal by using a lower fractional inspired oxygen concentration (FIO2)) can be achieved in the critically ill and appears to be safe. This approach has not been evaluated in a National Health Service setting. It is possible that permissive hypoxaemia may be beneficial to critically ill patients thus it requires robust evaluation.Methods and analysisTargeted OXygen therapY in Critical illness (TOXYC) is a feasibility randomised controlled trial (RCT) to evaluate whether recruiting patients to a study of permissive hypoxaemia is possible in the UK. It will also investigate biological mechanisms that may underlie the links between oxygenation and patient outcomes. Mechanically ventilated patients with respiratory failure will be recruited from critical care units at two sites and randomised (1:1 ratio) to an SpO2target of either 88%–92% or ≥96% while intubated with an endotracheal tube. Clinical teams can adjust FIO2and ventilator settings as they wish to achieve these targets. Clinical information will be collected before, during and after the intervention and blood samples taken to measure markers of systemic oxidative stress. The primary outcome of this study is feasibility, which will be assessed by recruitment rate, protocol adherence and withdrawal rates. Secondary outcomes will include a comparison of standard critical care outcome measures between the two intervention groups, and the measurement of biomarkers of systemic oxidative stress. The results will be used to calculate a sample size, likely number of sites and overall length of time required for a subsequent large multicentre RCT.Ethics and disseminationThis study was approved by the London - Harrow Research Ethics Committee on 2 November 2017 (REC Reference 17/LO/1334) and received HRA approval on 13 November 2017. Results from this study will be disseminated in peer-reviewed journals, at medical and scientific meetings, in the NIHR Journals Library and patient information websites.Trial registration numberNCT03287466; Pre-results.</jats:sec

The SmartTarget BIOPSY trial: A prospective, within-person randomised, blinded trial comparing the accuracy of visual-registration and MRI/ultrasound image-fusion targeted biopsies for prostate cancer risk stratification

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. Whether visual-registration targeting is sufficient or if augmentation with image-fusion software is needed is unknown. Objective: To assess concordance between the two methods. Design, Setting, and Participants: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3 to 5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. Intervention: The order of performing biopsies using visual-registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome Measurements and Statistical Analysis: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions. Results and Limitations: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy individually detected 80/93 (86%) of these cancers; each strategy detected 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 weeks) was observed. The key limitation was lack of parallel-group randomisation and limit on number of targeted cores. Conclusions: Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. Patient Summary: We compared two prostate cancer biopsy strategies: visual-registration and image-fusion. The combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009)

The SmartTarget Biopsy Trial: A Prospective, Within-person Randomised, Blinded Trial Comparing the Accuracy of Visual-registration and Magnetic Resonance Imaging/Ultrasound Image-fusion Targeted Biopsies for Prostate Cancer Risk Stratification

Background: Multiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. It is unknown whether visual-registration targeting is sufficient or augmentation with image-fusion software is needed. Objective: To assess concordance between the two methods. Design, setting, and participants: We conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3–5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. Intervention: The order of performing biopsies using visual registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome measurements and statistical analysis: The proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3 + 4 = 7, maximum cancer core length ≥4 mm; secondary outcome: Gleason pattern ≥4 + 3 = 7, maximum cancer core length ≥6 mm) detected by each method was compared using McNemar's test of paired proportions. Results and limitations: The two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy detected 80/93 (86%) of these cancers; each strategy identified 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea, and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 wk) was observed. The key limitations were lack of parallel-group randomisation and a limit on the number of targeted cores. Conclusions: Visual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. Patient summary: We compared two prostate cancer biopsy strategies: visual registration and image fusion. A combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed. Image-fusion results in a clinically significant prostate cancer detection rate were similar to those of visual registration performed by an experienced operator. Detection could be improved by 14% with no adverse effect on patient safety by adding image fusion to conventional visual-registration targeting

Mittheilungen aus dem pharmaceutischen Laboratorium

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Proactive referral to behavioral smoking cessation programs by healthcare staff: a systematic review

INTRODUCTION: Behavioral smoking cessation programs are an effective tool for quitting smoking, yet remain underused by smokers. Proactive referral may be a promising strategy for healthcare staff to connect smokers to such programs. The aim of this study was to gain insight into the effectiveness and implementability of proactive referral of smokers to behavioral smoking cessation programs by healthcare staff. METHODS: A systematic review was conducted using five databases. Effectiveness of proactive referral was defined as the proportion of referred smokers who enrolled in a behavioral smoking cessation program. To determine the implementability of proactive referral, measures of feasibility, acceptability, adoption and referral rates were included as variables of interest. Out of 6,686 screened records, 34 articles were eligible for review. A narrative synthesis approach was used. RESULTS: The majority of the included studies investigated proactive referral within an e-referral system, combined with one or more intervention components which enhance implementation. Overall, proactive referral resulted in higher enrolment rates, especially among low-income smokers, and was found to be feasible, adoptable, and acceptable to healthcare staff. E-referral systems performed better in terms of implementability compared to fax referral systems. About half of the studies were of good quality. Many studies lacked information which resulted in lower quality scores. CONCLUSIONS: The literature provides evidence that the proactive referral of smokers to behavioral smoking cessation programs by healthcare staff is effective and implementable across different settings. Based on the results, e-referral systems may be preferable to fax referral systems in terms of implementability. IMPLICATIONS: This systematic review demonstrated that proactive referral has the potential to increase the reach of smoking cessation programs and reduce inequalities in the access to such programs. In the selection and implementation of behavioral smoking cessation programs with a proactive referral component, stakeholders (e.g., policymakers, healthcare funders, and healthcare professionals) may benefit from taking different aspects of proactive referral systems into account, such as the type of proactive referral system used and additional strategies which can enhance the implementability of the system

Käsihygienian toteutuminen vuodeosaston lääkehoitohuoneessa

Opinnäytetyö koostuu kahdesta erillisestä osiosta; teoreettisesta viitekehyksestä ja havainnointitutkimuksesta. Käsihygieniaan tulee nykyisin kiinnittää enemmän huomiota, koska merkittävin yksittäinen keino estää infektioiden leviäminen on käsihygienian asianmukainen toteuttaminen. Lääkkeitä käsitellessä on ehdottoman tärkeää toteuttaa aseptiikkaa, jotta työntekijä välttää altistumisen lääkeaineille sekä lääkeaineet eivät kontaminoituisi. Tämä opinnäytetyö toteutettiin yhteistyössä projektina KiiltoClean Oy:n, Laurea-ammattikorkeakoulun ja Pirkanmaan sairaanhoitopiirin erään yhteistyöosaston kanssa. Projektiraportin tarkoituksena oli kuvata yhteistyöosaston hoitohenkilökunnan lääkehoitohuoneessa toteutunutta aseptista työskentelyä. Tavoitteena oli näyttöön perustuen lisätä tietoa käsihygieniasta ja sen toteutumisesta vuodeosaston lääkehoitohuoneessa. Projektiraportissa havainnoitiin 22,5 tuntia hoitohenkilökunnan aseptista toimintaa lääkehoitohuoneessa. Aineistonkeruumenetelmänä oli tarkkaileva havainnointi. Aineiston analyysissä käytettiin tutkittuun tietoon ja kokemusperäiseen näyttöön perustuvaa strukturoitua havainnointimatriisia, jossa oli 20 aseptiseen toimintaan liittyvää toimintoa. Toimintoja tarkasteltiin toteutumisen kannalta. Tuloksissa todettiin käsihygienian toteutumisen olevan kohtuullista ja aseptisessa toiminnassa havainnoitiin selkeitä puutteita. Automaattiannostelijaa käyttäneiden hoitotyöntekijöiden käsien desinfiointiaika oli keskimäärin 16 sekuntia. Lanka-annostelijan käyttäjistä saatu keskiarvo oli puolet alhaisempi, kahdeksan sekuntia. Oikeat työmenetelmät edistävät hyvän käsihygienian toteutumista. Hyvä käsihygienia, tavanomaiset varotoimet, oikeanlaiset työvälineet lääkkeenjaossa ja jatkuva koulutus auttavat aseptisen toiminnan toteutumisessa. Opinnäytetyön tuloksia voidaan hyödyntää terveydenhuoltoalalla.Implementing hand hygiene in a medication room on the ward This thesis consists of two separate parts: a theoretical framework and an observational study. Hand hygiene now requires greater attention, since the single most significant way to prevent the spread of infection is through a proper implementation of hand hygiene. When handling medicines it is essential to carry out aseptic precautions in order to avoid exposure to drug ingredients and to prevent contaminating the pharmaceuticals. This study was carried out as a project in cooperation with KiiltoClean Ltd, Laurea University of Applied Sciences, and a cooperation partner ward in the Pirkanmaa Hospital District. The purpose of the project report was to describe the aseptic procedures carried out by the nursing staff in the medication room of the cooperation partner ward. The aim was to use the evidence gained to provide additional information on hand hygiene and its implementation in the medication room on the ward. The project report covered 22.5 hours of observing the aseptic procedures carried out by the nursing staff in the medication room. The data was collected through observations. To analyse the data the authors applied a structured observation matrix, combining research-based and empirical evidence, covering 20 functions related to aseptic procedures. The results showed that the implementation of hand hygiene was at a moderate level and that evident limitations existed in aseptic procedures. The average time used for the hand disinfection by the nursing staff using automatic dispensers was 16 seconds. The average time spent by the nursing staff using manual dispensers was half as long as the time spent by the nursing staff using automatic dispensers, eight seconds. Correct working procedures promote good implementation of hand hygiene. Good hand hygiene, standard precautions, appropriate tools for the administration of medication, and professional development, help in the implementation of aseptic procedures. The results of this thesis can be used in the health sector