Summary Background Optimum surgical intervention for low-grade haemorrhoids is unknown. Haemorrhoidal artery ligation (HAL) has been proposed as an efficacious, safe therapy while rubber band ...ligation (RBL) is a commonly used outpatient treatment. We compared recurrence after HAL versus RBL in patients with grade II–III haemorrhoids. Methods This multicentre, open-label, parallel group, randomised controlled trial included patients from 17 acute UK NHS trusts. We screened patients aged 18 years or older presenting with grade II–III haemorrhoids. We excluded patients who had previously received any haemorrhoid surgery, more than one injection treatment for haemorrhoids, or more than one RBL procedure within 3 years before recruitment. Eligible patients were randomly assigned (in a 1:1 ratio) to either RBL or HAL with Doppler. Randomisation was computer-generated and stratified by centre with blocks of random sizes. Allocation concealment was achieved using a web-based system. The study was open-label with no masking of participants, clinicians, or research staff. The primary outcome was recurrence at 1 year, derived from the patient's self-reported assessment in combination with resource use from their general practitioner and hospital records. Recurrence was analysed in patients who had undergone one of the interventions and been followed up for at least 1 year. This study is registered with the ISRCTN registry, ISRCTN41394716. Findings From Sept 9, 2012, to May 6, 2014, of 969 patients screened, 185 were randomly assigned to the HAL group and 187 to the RBL group. Of these participants, 337 had primary outcome data (176 in the RBL group and 161 in the HAL group). At 1 year post-procedure, 87 (49%) of 176 patients in the RBL group and 48 (30%) of 161 patients in the HAL group had haemorrhoid recurrence (adjusted odds ratio aOR 2·23, 95% CI 1·42–3·51; p=0·0005). The main reason for this difference was the number of extra procedures required to achieve improvement (57 32% participants in the RBL group and 23 14% participants in the HAL group had a subsequent procedure for haemorrhoids). The mean pain 1 day after procedure was 3·4 (SD 2·8) in the RBL group and 4·6 (2·8) in the HAL group (difference −1·2, 95% CI −1·8 to −0·5; p=0·0002); at day 7 the scores were 1·6 (2·3) in the RBL group and 3·1 (2·4) in the HAL group (difference −1·5, −2·0 to −1·0; p<0·0001). Pain scores did not differ between groups at 21 days and 6 weeks. 15 individuals reported serious adverse events requiring hospital admission. One patient in the RBL group had a pre-existing rectal tumour. Of the remaining 14 serious adverse events, 12 (7%) were among participants treated with HAL and two (1%) were in those treated with RBL. Six patients had pain (one treated with RBL, five treated with HAL), three had bleeding not requiring transfusion (one treated with RBL, two treated with HAL), two in the HAL group had urinary retention, two in the HAL group had vasovagal upset, and one in the HAL group had possible sepsis (treated with antibiotics). Interpretation Although recurrence after HAL was lower than a single RBL, HAL was more painful than RBL. The difference in recurrence was due to the need for repeat bandings in the RBL group. Patients (and health commissioners) might prefer such a course of RBL to the more invasive HAL. Funding NIHR Health Technology Assessment programme.
We aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection.
We undertook a mixed ...prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set.
We analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points.
A clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care.
ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it ...prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities.This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations.We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.
Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected ...COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results.
We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%).
Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support.
ISRCTN registry, ISRCTN56149622, http://www.isrctn.com/ISRCTN28342533.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Between 2015 and 2020 the Alleviating Specific Phobias Experienced by Children Trial (ASPECT) was conducted in the UK to examine the non-inferiority of One-Session Treatment in comparison to ...Cognitive Behavioural Therapy based interventions for children and young people with specific phobias. A nested qualitative evaluation was conducted as part of this trial to examine the acceptability of One-Session Treatment. Qualitative interviews were conducted with children and young people taking part in the trial, their parents/guardians, and clinicians delivering the intervention, about their experiences and the acceptability of One Session Treatment. Interviews were digitally recorded and transcribed verbatim. Analysis followed a qualitative framework approach, a widely used method of analysing primary qualitative data pertaining to healthcare practices with policy relevance. Stakeholder groups found One Session Treatment to be an acceptable intervention and barriers and facilitators for its implementation into services were also identified. Potential barriers included challenges to patient flow and treatment scepticism, whilst facilitators included adopting a child-centred approach, child readiness and suitability, opportunity for increased momentum, parental support and involvement, and proximal and distal gains. For One Session Treatment’s successful implementation into services, consideration of these barriers is needed and suitability guidance for its use in this population should be developed. Further research exploring children and young people’s experiences of receiving Cognitive Behavioural Therapy and its acceptability in comparison to One Session Treatment would be welcomed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Between 2015 and 2020 the Alleviating Specific Phobias Experienced by Children Trial (ASPECT) was conducted in the UK to examine the non-inferiority of One-Session Treatment in comparison to ...Cognitive Behavioural Therapy based interventions for children and young people with specific phobias. A nested qualitative evaluation was conducted as part of this trial to examine the acceptability of One-Session Treatment. Qualitative interviews were conducted with children and young people taking part in the trial, their parents/guardians, and clinicians delivering the intervention, about their experiences and the acceptability of One Session Treatment. Interviews were digitally recorded and transcribed verbatim. Analysis followed a qualitative framework approach, a widely used method of analysing primary qualitative data pertaining to healthcare practices with policy relevance. Stakeholder groups found One Session Treatment to be an acceptable intervention and barriers and facilitators for its implementation into services were also identified. Potential barriers included challenges to patient flow and treatment scepticism, whilst facilitators included adopting a child-centred approach, child readiness and suitability, opportunity for increased momentum, parental support and involvement, and proximal and distal gains. For One Session Treatment's successful implementation into services, consideration of these barriers is needed and suitability guidance for its use in this population should be developed. Further research exploring children and young people's experiences of receiving Cognitive Behavioural Therapy and its acceptability in comparison to One Session Treatment would be welcomed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ObjectivesTo explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.DesignQualitative interviews analysed using thematic analysis.Setting and participantsFive ...professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022. Participants were identified via their institutional web page, existing contacts or social media (eg, X, formerly known as Twitter).ResultsProfessionals viewed that diversity is not currently considered in all early-phase clinical trials but felt that it should always be taken into account. Such trials are primarily undertaken at a small number of centres, thus limiting the populations they can access. Referrals from clinicians based in the community may increase diversity; however, those referred are often not from underserved groups. Referrals may be hindered by the extra resources required to approach and recruit underserved groups and participants often having to undertake ‘self-driven’ referrals. Patient and public representatives stated that diversity is important in research staff and that potential participants should be informed of the need for diversity. Those from underserved groups may require clarification regarding the potential harms of a treatment, even if these are unknown. Education may improve awareness and perception of early-phase clinical trials. We provide 14 recommendations to improve diversity in early-phase clinical trials.ConclusionsDiversity should be considered in all early-phase trials. Consideration is required regarding the extent of diversity and how it is addressed. The increased resources needed to recruit those from underserved groups may warrant funders to increase the funds to support the recruitment of such participants. The potential harms and societal benefits of the research should be presented to potential participants in a balanced but accurate way to increase transparency.
Randomised controlled trials are designed to assess the superiority, equivalence or non-inferiority of a new health technology, but which trial design should be used is not always obvious in ...practice. In particular, when using equivalence or non-inferiority designs, multiple outcomes of interest may be important for the success of a trial, despite the fact that usually only a single primary outcome is used to design the trial. Benefit-risk methods are used in the regulatory clinical trial setting to assess multiple outcomes and consider the trade-off of the benefits against the risks, but are not regularly implemented in publicly funded trials.
The aim of the project is to aid the design of clinical trials with multiple outcomes of interest by defining when each trial design is appropriate to use and identifying when to use benefit-risk methods to assess outcome trade-offs (qualitatively or quantitatively) in a publicly funded trial setting.
A range of methods was used to elicit expert opinion to answer the project objectives, including a web-based survey of relevant researchers, a rapid review of current literature and a 2-day consensus workshop of experts (in 2019).
We created a list of 19 factors to aid researchers in selecting the most appropriate trial design, containing the following overarching sections: population, intervention, comparator, outcomes, feasibility and perspectives. Six key reasons that indicate a benefit-risk method should be considered within a trial were identified: (1) when the success of the trial depends on more than one outcome; (2) when important outcomes within the trial are in competing directions (i.e. a health technology is better for one outcome, but worse for another); (3) to allow patient preferences to be included and directly influence trial results; (4) to provide transparency on subjective recommendations from a trial; (5) to provide consistency in the approach to presenting results from a trial; and (6) to synthesise multiple outcomes into a single metric. Further information was provided to support the use of benefit-risk methods in appropriate circumstances, including the following: methods identified from the review were collated into different groupings and described to aid the selection of a method; potential implementation of methods throughout the trial process were provided and discussed (with examples); and general considerations were described for those using benefit-risk methods. Finally, a checklist of five pieces of information that should be present when reporting benefit-risk methods was defined, with two additional items specifically for reporting the results.
These recommendations will assist research teams in selecting which trial design to use and deciding whether or not a benefit-risk method could be included to ensure research questions are answered appropriately. Additional information is provided to support consistent use and clear reporting of benefit-risk methods in the future. The recommendations can also be used by funding committees to confirm that appropriate considerations of the trial design have been made.
This research was limited in scope and should be considered in conjunction with other trial design methodologies to assess appropriateness. In addition, further research is needed to provide concrete information about which benefit-risk methods are best to use in publicly funded trials, along with recommendations that are specific to each method.
The rapid review is registered as PROSPERO CRD42019144882.
Funded by the Medical Research Council UK and the National Institute for Health and Care Research as part of the Medical Research Council-National Institute for Health and Care Research Methodology Research programme.
What is the purpose of clinical trial monitoring? Love, Sharon B; Yorke-Edwards, Victoria; Ward, Elizabeth ...
Current controlled trials in cardiovascular medicine,
10/2022, Letnik:
23, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The sources of information on clinical trial monitoring do not give information in an accessible language and do not give detailed guidance. In order to enable communication and to build clinical ...trial monitoring tools on a strong easily communicated foundation, we identified the need to define monitoring in accessible language.
In a three-step process, the material from sources that describe clinical trial monitoring were synthesised into principles of monitoring. A poll regarding their applicability was run at a UK national academic clinical trials monitoring meeting.
The process derived 5 key principles of monitoring: keeping participants safe and respecting their rights, having data we can trust, making sure the trial is being run as it was meant to be, improving the way the trial is run and preventing problems before they happen.
From the many sources mentioning monitoring of clinical trials, the purpose of monitoring can be summarised simply as 5 principles. These principles, given in accessible language, should form a firm basis for discussion of monitoring of clinical trials.
Group interventions are interventions delivered to groups of people rather than to individuals and are used in healthcare for mental health recovery, behaviour change, peer support, self-management ...and/or health education. Evaluating group interventions in randomised controlled trials (RCTs) presents trialists with a set of practical problems, which are not present in RCTs of one-to-one interventions and which may not be immediately obvious.
Case-based approach summarising Sheffield trials unit's experience in the design and implementation of five group interventions. We reviewed participant recruitment and attrition, facilitator training and attrition, attendance at the group sessions, group size and fidelity aspects across five RCTs.
Median recruitment across the five trials was 3.2 (range 1.7-21.0) participants per site per month. Group intervention trials involve a delay in starting the intervention for some participants, until sufficient numbers are available to start a group. There was no evidence that the timing of consent, relative to randomisation, affected post-randomisation attrition which was a matter of concern for all trial teams. Group facilitator attrition was common in studies where facilitators were employed by the health system rather than the by the grant holder and led to the early closure of one trial; research sites responded by training 'back-up' and new facilitators. Trials specified that participants had to attend a median of 62.5% (range 16.7%-80%) of sessions, in order to receive a 'therapeutic dose'; a median of 76.7% (range 42.9%-97.8%) received a therapeutic dose. Across the five trials, 75.3% of all sessions went ahead without the pre-specified ideal group size. A variety of methods were used to assess the fidelity of group interventions at a group and individual level across the five trials.
This is the first paper to provide an empirical basis for planning group intervention trials. Investigators should expect delays/difficulties in recruiting groups of the optimal size, plan for both facilitator and participant attrition, and consider how group attendance and group size affects treatment fidelity.
ISRCTN17993825 registered on 11/10/2016, ISRCTN28645428 registered on 11/04/2012, ISRCTN61215213 registered on 11/05/2011, ISRCTN67209155 registered on 22/03/2012, ISRCTN19447796 registered on 20/03/2014.
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