Staff-led interventions for improving oral hygiene in patients following stroke

Background For people with limitations due to neurological conditions such as stroke, the routine practice of oral care may become a challenge. Evidence-based supported oral care intervention is essential for this patient group. Objectives To compare the effectiveness of staff-led oral care interventions with standard care for ensuring oral hygiene for individuals after a stroke. Search strategy We searched the trials registers of the Cochrane Stroke Group and Oral Health Group (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to February 2006), CINAHL (1982 to February 2006), Research Findings Electronic Register (February 2006), National Research Register (Issue 1, 2006), ISI Science and Technology Proceedings (August 2005), Dissertation Abstracts and Conference Papers Index (August 2005). We scanned reference lists from relevant papers and contacted authors and researchers in the field. Selection criteria We identified randomised controlled trials that evaluated one or more interventions designed to improve oral hygiene. Trials based on a mixed population were included, provided it was possible to extract the data specific to the individuals post stroke. Data collection and analysis Two review authors independently classified identified trials according to the inclusion and exclusion criteria, assessed the trial quality and extracted data. Clarification was sought from study authors when required. Main results Eight eligible randomised controlled trials were identified but only one provided stroke-specific information. It compared an oral health care education training programme (OHCE) delivered to nursing home care assistants to delayed training intervention in the control group. Comparisons were made at one and six months after the intervention, using the primary outcome measures dental plaque and denture plaque, and three secondary outcomes. The data available for the 67 individuals with a stroke (obtained from the larger cluster randomised controlled trial) showed that denture plaque scores were significantly reduced up to six months (P &lt; 0.00001) after the intervention. Staff knowledge (P = 0.0008) and attitudes (P = 0.0001) towards oral care also improved significantly. Authors' conclusions Based on one study with a small number of stroke survivors, providing oral care training for carers in a nursing home setting improves their knowledge of and attitudes towards the provision of oral care. In turn, residents' dentures were cleaner, though other oral hygiene measures did not change. Further evidence relating to oral care interventions is severely lacking, in particular with reference to care in hospital for those following stroke. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2011, Issue 7. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.</p

Defining high probability when making a diagnosis of asthma in primary care: a mixed methods consensus workshop::a mixed methods consensus workshop

Objectives Making the diagnosis of asthma is challenging. Guidelines recommend that clinicians identify a group at ‘high probability’ of asthma. ‘High probability’, however, is not numerically defined giving rise to uncertainty. The aim of this work was to build consensus on what constitutes a ‘high probability’ of asthma in primary care. ‘High probability’ was defined as the probability threshold at which there is enough information to make a firm diagnosis of asthma and a subsequent negative test would not alter that opinion (assumed to be a false negative).Design Mixed methods studySetting A consensus workshop using modified Nominal Group Technique was held during an international respiratory conference.Participants International conference attendees eligible if they had knowledge/experience of working in primary care, respiratory medicine and spoke English.Methods Participants took part in facilitated discussions and voted over three rounds on what constituted a high probability of asthma diagnosis. The workshop was audio-recorded, transcribed and qualitatively analysed.Results Based on final votes, the mean value for a high probability of asthma in primary care was 75% (SD 7.6), representing a perceived trade-off between limiting the number of false positives (more likely if a lower threshold was used) and pragmatism on the basis that first-line preventive therapies (i.e. low-dose inhaled corticosteroids) are relatively low risk. The need to review response to treatment was strongly emphasised for detecting non-responders and reviewing the diagnosis. Conclusion A consensus probability of 75% was the threshold at which the primary care participants in this workshop felt confident to establish the diagnosis of asthma, albeit with the caveat that a review of treatment response was essential. Contextual factors including availability and timing of tests and the ease with which patients could be reviewed influenced participants decision making.<br/

Prophylactic zoledronic acid therapy to prevent or modify Paget’s disease of bone progression in adults with SQSTM1 mutations: the ZiPP RCT

Background:Paget’s disease of bone is characterised by focal abnormalities of bone turnover resulting in various complications. It often presents at an advanced stage with irreversible bone damage. At this point, the symptomatic benefits of treatment are blunted. Paget’s disease of bone has a strong genetic component and the most important susceptibility gene is SQSTM1. Carriers of SQSTM1 mutations have more severe disease with an earlier age of onset than non-carriers and about 80% develop Paget’s disease of bone by the seventh decade.Objectives:The primary objective was to determine if zoledronic acid could prevent new Paget’s disease of bone-like bone lesions in SQSTM1 mutation carriers. Secondary objectives were to assess if zoledronic acid could: modify existing Paget’s disease of bone lesions, markers of bone turnover, quality of life, bone pain, anxiety, depression or the risk of complications.Design:This was a multicentre, double-blind placebo-controlled trial. Genetic screening of the SQSTM1 gene was offered to people with a family history of Paget’s disease of bone, identifying 222 mutation carriers who consented to participate. At baseline, a radionuclide bone scan was performed; biochemical markers of bone turnover were measured and questionnaires on pain, quality of life and mental health were completed. Participants completed annual biochemical markers measurements and questionnaires. Adverse events were recorded on a continuous basis. At the end of study, the bone scan was repeated, along with biochemical markers and questionnaires.Setting:This was a multicentre trial that was conducted at 27 secondary care referral centres for bone disease in 7 countries. All the visits were conducted within a secondary healthcare setting.Participants Interventions:Participants were randomly allocated to receive a single infusion of the bisphosphonate zoledronic acid 5 mg or an identical placebo.Main outcome measures:The study’s primary outcome measure was defined as the total number of participants who developed new bone lesions on radionuclide bone scans with the characteristics of PDB between the baseline visit and the final end-of-study visit. The secondary outcomes included the number of new PDB bone lesions on radionuclide bone scans, change in the activity of existing PDB bone lesions at the end of study assessed by radionuclide scans; changes in plasma type I collagen C-telopeptides (CTX); plasma procollagen type I amino-terminal propeptide (PINP); serum bone-specific alkaline phosphatase (BAP); quality of life assessed by SF-36, BPI, HADS questionnaires; the presence and severity of localized bone pain assessed by the BPI pain manikin; and the development of PDB-related skeletal events (PDRSE) in SQSTM1 mutation carriers including new lesions, complications (fractures, deformity), or the need for treatment of PDB.Methods:This was a multicentre, double-blind placebo-controlled trial. Genetic screening of the SQSTM1 gene was offered to people with a family history of Paget’s disease of bone, identifying 222 mutation carriers who consented to participate. At baseline, a radionuclide bone scan was performed; biochemical markers of bone turnover were measured and questionnaires on pain, quality of life and mental health were completed. Participants were randomly allocated to receive a single infusion of the bisphosphonate zoledronic acid 5 mg or an identical placebo. Participants completed annual biochemical markers measurements and questionnaires. Adverse events were recorded on a continuous basis. At the end of study, the bone scan was repeated, along with biochemical markers and questionnaires.Results:At baseline, 21/222 individuals (9.5%) had evidence of Paget’s disease of bone on bone scans. In the placebo group, 2/90 individuals (2.2%) developed new bone lesions compared with 0/90 (0%) in the zoledronic acid group (odds ratio 0.41, 95% confidence interval 0.00 to 3.43; p = 0.25). Eight participants in the placebo group had a poor outcome (new/unchanged/progressing lesions) compared with none in the zoledronic acid group (odds ratio 0.08, 95% confidence interval 0.00 to 0.42; p = 0.003). With placebo, 1/29 (3.4%) lesions disappeared compared with 13/15 (86.6%) with zoledronic acid (p &lt; 0.0001). One participant allocated to placebo required treatment with zoledronic acid due to a complication of Paget’s disease of bone. Significant reductions were observed for serum C-terminal telopeptide (p &lt; 0.0001), bone-specific alkaline phosphatase (p = 0.0003) and N-terminal propeptide of type I procollagen (p &lt; 0.0001) in the zoledronic acid group compared with placebo. There was no significant difference between groups in quality of life, pain, anxiety or depression.Conclusion:Genetic testing for SQSTM1 mutations coupled with bone scan examination can detect early Paget’s disease of bone in those with a family history of the disorder and zoledronic acid treatment can favourably modify its evolution.The study had some limitations. First, 9.5% of participants already had Paget’s disease of bone, reducing power. Second, only two participants developed new lesions compared to the 15% expected. The small number of events meant the study was underpowered for the primary outcome and we were unable to adjust analyses for co-variates or family clustering.An extended follow-up in the zoledronic acid in the prevention of Paget’s disease – long-term extension study is in progress and will provide valuable information on the duration of effects of a single zoledronic acid infusion. It will be important to consider a health economic analysis to model the effects of genetic testing, scanning and zoledronic acid treatment, to evaluate long-term clinical and symptomatic benefits.<br/

GALA:an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

BACKGROUND: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. METHODS/DESIGN: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free (including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00525237

Systematic review of clinical prediction models to support the diagnosis of asthma in primary care

Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in nonspecialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians

A survey on UK researchers’ views regarding their experiences with the de-identification, anonymisation, release methods and re-identification risk estimation for clinical trials datasets

Background: There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community. However, there is no standardised set of recommendations on how to anonymise and prepare clinical trials datasets for sharing, whilst an ever-increasing number of anonymised datasets are becoming available for secondary research. Our ‎aim was to explore the current views and experiences of researchers in the UK about de-identification, anonymisation, release methods and re-identification risk estimation for clinical trials datasets. Methods: We used an online exploratory cross-sectional descriptive survey that consisted of both open-ended and closed questions. Results: We had 38 responses to invitation from June 2022 to October 2022. 35 participants (92%) used internal documentation and/or published guidance to de-identify/anonymise clinical trials datasets. De-identification followed by anonymisation and then fulfilling data holders’ requirements before access was granted (controlled access) was the most common process for releasing the datasets as reported by 18 (47%) participants. Eleven participants (29%) had previous knowledge of re-identification risk estimation, but they did not use any of the methodologies. Experiences in the process of de-identifying/anonymising the datasets and maintaining such datasets were mostly negative, the main reported issues were: lack of resources, guidance, and training.Conclusions: The majority of responders reported using documented processes for de-identification and anonymization. However, our survey results clearly indicate that there are still gaps in the areas of guidance, resources and training to fulfil sharing requests of de-identified/anonymised datasets, and that re-identification risk estimation is an underdeveloped area

Determining a risk-proportionate approach to the validation of statistical programming for clinical trials

Background: The contribution of the statistician to the design and analysis of a clinical trial is acknowledged as essential. Ability to reconstruct the statistical contribution to a trial requires rigorous and transparent documentation as evidenced by the reproducibility of results. The process of validating statistical programmes is a key requirement. While guidance relating to software development and life cycle methodologies details steps for validation by information systems developers, there is no guidance applicable to programmes written by statisticians. We aimed to develop a risk-based approach to the validation of statistical programming that would support scientific integrity and efficient resource use within clinical trials units. // Methods: The project was embedded within the Information Systems Operational Group and the Statistics Operational Group of the UK Clinical Research Collaboration Registered Clinical Trials Unit network. Members were asked to share materials relevant to validation of statistical programming. A review of the published literature, regulatory guidance and knowledge of relevant working groups was undertaken. Surveys targeting the Information Systems Operational Group and Statistics Operational Group were developed to determine current practices across the Registered Clinical Trials Unit network. A risk-based approach was drafted and used as a basis for a workshop with representation from statisticians, information systems developers and quality assurance managers (n = 15). The approach was subsequently modified and presented at a second, larger scale workshop (n = 47) to gain a wider perspective, with discussion of content and implications for delivery. The approach was revised based on the discussions and suggestions made. The workshop was attended by a member of the Medicines for Healthcare products Regulatory Agency Inspectorate who also provided comments on the revised draft. // Results: Types of statistical programming were identified and categorised into six areas: generation of randomisation lists; programmes to explore/understand the data; data cleaning, including complex checks; derivations including data transformations; data monitoring; or interim and final analysis. The risk-based approach considers each category of statistical programme against the impact of an error and its likelihood, whether the programming can be fully prespecified, the need for repeated use and the need for reproducibility. Approaches to the validation of programming within each category are proposed. // Conclusion: We have developed a risk-based approach to the validation of statistical programming. It endeavours to facilitate the implementation of targeted quality assurance measures while making efficient use of limited resources

Post stroke intervention trial in fatigue (POSITIF):Randomised multicentre feasibility trial

OBJECTIVE: To test the feasibility of a telephone delivered intervention, informed by cognitive behavioural principles, for post-stroke fatigue, and estimated its effect on fatigue and other outcomes. DESIGN: Randomised controlled parallel group trial. SETTING: Three Scottish stroke services. SUBJECTS: Stroke survivors with fatigue three months to two years post-stroke onset. INTERVENTIONS: Seven telephone calls (fortnightly then a ‘booster session’ at 16 weeks) of a manualised intervention, plus information about fatigue, versus information only. MAIN MEASURES: Feasibility of trial methods, and collected outcome measures (fatigue, mood, anxiety, social participation, quality of life, return to work) just before randomisation, at the end of treatment (four months after randomisation) and at six months after randomisation. RESULTS: Between October 2018 and January 2020, we invited 886 stroke survivors to participate in postal screening: 188/886 (21%) returned questionnaires and consented, of whom 76/188 (40%) were eligible and returned baseline forms; 64/76 (84%) returned six month follow-up questionnaires. Of the 39 allocated the intervention, 23 (59%) attended at least four sessions. At six months, there were no significant differences between the groups (adjusted mean differences in Fatigue Assessment Scale −0.619 (95% CI −4.9631, 3.694; p = 0.768), the Generalised Anxiety Disorder 7 −0.178 (95% CI −3.823, 3.467, p = 0.92), and the Patient Health Questionnaire −0.247 (95% CI −2.935, 2.442, p = 0.851). There were no between-group differences in quality of life, social participation or return to work. CONCLUSION: Patients can be recruited to a trial of this design. These data will inform the design of further trials in post-stroke fatigue