Background
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the resulting COVID‐19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to ...identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point‐of‐care antigen and molecular tests to detect current SARS‐CoV‐2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory‐based diagnostic methods, with the aim of reducing household and community transmission.
Objectives
To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests to determine if a person presenting in the community or in primary or secondary care has current SARS‐CoV‐2 infection.
Search methods
On 25 May 2020 we undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions.
Selection criteria
We included studies of people with suspected current SARS‐CoV‐2 infection, known to have, or not to have SARS‐CoV‐2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established clinical diagnostic criteria).
Data collection and analysis
Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS‐2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular‐based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer.
Main results
We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS‐CoV‐2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in‐house antigen test. Five of the studies included were only available as preprints.
We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over‐sampling of samples with confirmed COVID‐19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT‐PCR to confirm the absence of COVID‐19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations.
Antigen tests
Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test.
Rapid molecular assays
Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID‐19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%).
Individual tests
We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of −2.8% (95% CI −6.4 to 0.8))
Authors' conclusions
This review identifies early‐stage evaluations of point‐of‐care tests for detecting SARS‐CoV‐2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID‐19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT‐PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice.
Prospective and comparative evaluations of rapid tests for COVID‐19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point‐of‐care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.
Background Severe allergic rhinitis uncontrolled by pharmacotherapy can adversely affect quality of life. Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have demonstrated ...effectiveness in this patient group; however, it remains uncertain which route of administration is more effective. Objectives We sought to update existing systematic reviews on the clinical effectiveness of SCIT and SLIT versus placebo, to undertake a systematic review of head-to-head trials, and to compare the relative effectiveness of SCIT and SLIT in an adjusted indirect comparison. Methods Standard systematic review methods aimed at minimizing bias were used. Double-blind, randomized, placebo-controlled trials of SCIT or SLIT or trials of SCIT versus SLIT were included. Meta-analysis and indirect comparison meta-analysis with meta-regression were performed. Results Updated meta-analyses confirmed statistically significant benefits for SCIT and SLIT compared with placebo in adults and, to a lesser extent, in children. Only 1 head-to-head trial met the inclusion criteria; both this and the indirect comparisons did not provide conclusive results in favor of either SCIT or SLIT based on symptom-medication or quality-of-life scores. There was a trend toward favoring SCIT for symptom and medication scores. Conclusions Although there is clear evidence of effectiveness of both SCIT and SLIT, superiority of one mode of administration over the other could not be consistently demonstrated through indirect comparison, and further research is needed to establish the comparative effectiveness of SCIT versus SLIT.
Evidence-based interventions are often unavailable in everyday clinical settings. This may partly reflect practitioners’ assumptions that research evidence does not reflect “real-world” conditions. ...To examine this further, we systematically assessed the clinical effectiveness of parent management training (PMT) for the treatment of child disruptive behavior across different real-world practice contexts. We identified 28 relevant randomized controlled trials from a systematic search of electronic bibliographic databases and conducted a meta-analysis of child outcomes across trials. Planned subgroup analyses involved comparisons between studies grouped according to individual real-world practice criteria and total real-world practice criteria scores, reflecting the extent to which PMT was delivered by non-specialist therapists, to a clinic-referred population, in a routine setting, and as part of a routine service. Meta-analysis revealed a significant overall advantage for PMT compared with waitlist control conditions. Subgroup analyses did not demonstrate significant differences in effect size estimates according to the total number of real-world practice criteria met by studies. Moreover, no consistent relationships were found between specific practice criteria and effect size estimates. In conclusion, PMT appears to be an effective treatment for children with disruptive behavior problems. There was no clear evidence that conducting PMT in real-world practice contexts is a deterrent to achieving effective child behavior outcomes, although relative advantage to “usual care” was not directly examined and the power of the analysis was limited as a result of significant heterogeneity. More research is needed to investigate whether this finding is generalizable to other psychological interventions. Suggestions are also made for developing more differentiated criteria to assist with evaluating the specific applicability of research evidence to different care providers.
Abstract
Aims
We assessed the performance of modelsf (risk scores) for predicting recurrence of atrial fibrillation (AF) in patients who have undergone catheter ablation.
Methods and results
...Systematic searches of bibliographic databases were conducted (November 2018). Studies were eligible for inclusion if they reported the development, validation, or impact assessment of a model for predicting AF recurrence after ablation. Model performance (discrimination and calibration) measures were extracted. The Prediction Study Risk of Bias Assessment Tool (PROBAST) was used to assess risk of bias. Meta-analysis was not feasible due to clinical and methodological differences between studies, but c-statistics were presented in forest plots. Thirty-three studies developing or validating 13 models were included; eight studies compared two or more models. Common model variables were left atrial parameters, type of AF, and age. Model discriminatory ability was highly variable and no model had consistently poor or good performance. Most studies did not assess model calibration. The main risk of bias concern was the lack of internal validation which may have resulted in overly optimistic and/or biased model performance estimates. No model impact studies were identified.
Conclusion
Our systematic review suggests that clinical risk prediction of AF after ablation has potential, but there remains a need for robust evaluation of risk factors and development of risk scores.
Problematic scarring remains a challenging aspect to address in the treatment of burns and can significantly affect the quality of life of the burn survivor. At present, there are few treatments ...available in the clinic to control adverse scarring, but experimental pharmacological anti-scarring strategies are now beginning to emerge. Their comparative success must be based on objective measurements of scarring, yet currently the clinical assessment of scars is not carried out systematically and is mostly based on subjective review of patients. However, several techniques and devices are being introduced that allow objective analysis of the burn scar. The aim of this article is to evaluate various objective measurement tools currently available and recommend a useful panel that is suitable for use in clinical trials of anti-scarring therapies.
A systematic literature search was done using the Web of Science, PubMed and Cochrane databases. The identified devices were then classified and grouped according to the parameters they measured. The tools were then compared and assessed in terms of inter- and intra-rater reproducibility, ease of use and cost.
After duplicates were removed, 5062 articles were obtained in the search. After further screening, 157 articles which utilised objective burn scar measurement systems or tools were obtained. The scar measurement devices can be broadly classified into those measuring colour, metric variables, texture, biomechanical properties and pathophysiological disturbances.
Objective scar measurement tools allow the accurate and reproducible evaluation of scars, which is important for both clinical and scientific use. However, studies to evaluate their relative performance and merits of these tools are scarce, and there remain factors, such as itch and pain, which cannot be measured objectively. On reviewing the available evidence, a panel of devices for objective scar measurement is recommended consisting of the 3D cameras (Eykona/Lifeviz/Vectra H1) for surface area and volume, DSM II colorimeter for colour, Dermascan high-frequency ultrasound for scar thickness and Cutometer for skin elasticity and pliability.
BackgroundPeople in underserved groups have higher rates of tuberculosis (TB) and poorer treatment outcomes compared with people with no social risk factors.ObjectivesThis scoping review aimed to ...identify interventions that improve TB treatment adherence or completion rates.Eligibility criteriaStudies of any design focusing on interventions to improve adherence or completion of TB treatment in underserved populations in low incidence countries.Sources of evidenceMEDLINE, Embase and Cochrane CENTRAL were searched (January 2015 to December 2023).Charting methodsPiloted data extraction forms were used. Findings were tabulated and reported narratively. Formal risk of bias assessment or synthesis was not undertaken.Results47 studies were identified. There was substantial heterogeneity in study design, population, intervention components, usual care and definition of completion rates. Most studies were in migrants or refugees, with fewer in populations with other risk factors (eg, homelessness, imprisonment or substance abuse). Based on controlled studies, there was limited evidence to suggest that shorter treatment regimens, video-observed therapy (compared with directly observed therapy), directly observed therapy (compared with self-administered treatment) and approaches that include tailored health or social support beyond TB treatment may lead to improved outcomes. This evidence is mostly observational and subject to confounding. There were no studies in Gypsy, Roma and Traveller populations, or individuals with mental health disorders and only one in sex workers. Barriers to treatment adherence included a lack of knowledge around TB, lack of general health or social support and side effects. Facilitators included health education, trusted relationships between patients and healthcare staff, social support and reduced treatment duration.ConclusionsThe evidence base is limited, and few controlled studies exist. Further high-quality research in well-defined underserved populations is needed to confirm the limited findings and inform policy and practice in TB management. Further qualitative research should include more people from underserved groups.
Chronic migraine is a debilitating headache disorder that has significant impact on quality of life. Stimulation of peripheral nerves is increasingly being used to treat chronic refractory pain ...including headache disorders. This systematic review examines the effectiveness and adverse effects of occipital nerve stimulation (ONS) for chronic migraine.
Databases, including the Cochrane Library, MEDLINE, EMBASE, CINAHL and clinical trial registers were searched to September 2014. Randomized controlled trials (RCTs), other controlled and uncontrolled observational studies and case series (n≥ 10) were eligible. RCTs were assessed using the Cochrane risk of bias tool. Meta-analysis was carried out using a random-effects model. Findings are presented in summary tables and forest plots.
Five RCTs (total n=402) and seven case series (total n=115) met the inclusion criteria. Pooled results from three multicenter RCTs show that ONS was associated with a mean reduction of 2.59 days (95% CI 0.91 to 4.27, I2=0%) of prolonged, moderate to severe headache per month at 3 months compared with a sham control. Results for other outcomes generally favour ONS over sham controls but quantitative analysis was hampered by incomplete publication and reporting of trial data. Lead migration and infections are common and often require revision surgery. Open-label follow-up of RCTs and case series suggest long-term effectiveness can be maintained in some patients but evidence is limited.
While the effectiveness of ONS compared to sham control has been shown in multiple RCTs, the average effect size is modest and may be exaggerated by bias as achieving effective blinding remains a methodological challenge. Further measures to reduce the risk of adverse events and revision surgery are needed.
this systematic review is an update and expanded work of part of a broader review registered with PROSPERO. Registration No. CRD42012002633.
Background
The traditional cancer follow‐up (FU) model for cancer survivors is by scheduled clinic appointments; however, this is not tailored to patient needs and is becoming unsustainable. ...Patient‐initiated follow‐up (PIFU) may be a more effective and flexible alternative. This systematic review aims to analyse all existing evidence from randomised controlled trials (RCTs) on the effectiveness of PIFU compared with other FU models that include routinely scheduled appointments in adults who have been treated with curative intent for any type of cancer.
Methods
Standard systematic review methodology aimed at limiting bias was used for study identification, selection and data extraction. MEDLINE, Embase, CINAHL, the Cochrane Database of Systematic Reviews and Epistemonikos were searched for systematic reviews to March 2022, and Cochrane CENTRAL was searched for RCTs from 2018 (April 2023). Ongoing trial registers were searched (WHO ICTRP, ClinicalTrials.gov, April 2023). Eligible studies were randomised controlled trials comparing PIFU with an alternative FU model in adult cancer survivors. Risk of bias assessment was via the Cochrane risk of bias tool‐2. Meta‐analysis was precluded by clinical heterogeneity and results were reported narratively.
Results
Ten RCTs were included (six breast, two colorectal, one endometrial cancer and one melanoma, total n = 1754); all studies had risk of bias concerns, particularly relating to how missing data were handled, and populations were unlikely to be representative. Limited findings in breast cancer suggested that type of FU does not affect recurrence detection or patient‐related outcomes, while PIFU may reduce the number of clinic visits. Adding patient‐led surveillance to routine FU may increase melanoma detection. Evidence for other types of cancer is too limited to draw firm conclusions.
Conclusions
PIFU may be a viable FU model in breast cancer, but further research is needed for other types of cancer and on long‐term outcomes. A protocol was registered with PROSPERO (CRD42020181424).
Non-union affects up to 10% of fractures and is associated with substantial morbidity. There is currently no single effective therapy for the treatment or prevention of non-union. Potential ...treatments are currently selected for clinical trials based on results from limited animal studies, with no attempt to compare results between therapies to determine which have the greatest potential to treat non-union.
The aim of this systematic review was to define the range of therapies under investigation at the preclinical stage for the prevention or treatment of fracture non-union. Additionally, through meta-analysis, it aimed to identify the most promising therapies for progression to clinical investigation.
MEDLINE and Embase were searched from 1St January 2004 to 10th April 2017 for controlled trials evaluating an intervention to prevent or treat fracture non-union. Data regarding the model used, study intervention and outcome measures were extracted, and risk of bias assessed.
Of 5,171 records identified, 197 papers describing 204 therapies were included. Of these, the majority were only evaluated once (179/204, 88%), with chitosan tested most commonly (6/204, 3%). Substantial variation existed in model design, length of survival and duration of treatment, with results poorly reported. These factors, as well as a lack of consistently used objective outcome measures, precluded meta-analysis.
This review highlights the variability and poor methodological reporting of current non-union research. The authors call for a consensus on the standardisation of animal models investigating non-union, and suggest journals apply stringent criteria when considering animal work for publication.
Background and aimsLittle is known about the relationship between inflammatory bowel disease (IBD) and body image. The aim of this systematic review was to summarise the evidence on body image ...dissatisfaction in patients with IBD across four areas: (1) body image tools, (2) prevalence, (3) factors associated with body image dissatisfaction in IBD and (4) association between IBD and quality of life.MethodsTwo reviewers screened, selected, quality assessed and extracted data from studies in duplicate. EMBASE, MEDLINE, PsycINFO and Cochrane CENTRAL were searched to April 2018. Study design–specific critical appraisal tools were used to assess risk of bias. Narrative analysis was undertaken due to heterogeneity.ResultsFifty-seven studies using a body image tool were included; 31 for prevalence and 16 and 8 for associated factors and association with quality of life, respectively. Studies reported mainly mean or median scores. Evidence suggested female gender, age, fatigue, disease activity and steroid use were associated with increased body image dissatisfaction, which was also associated with decreased quality of life.ConclusionThis is the first systematic review on body image in patients with IBD. The evidence suggests that body image dissatisfaction can negatively impact patients, and certain factors are associated with increased body image dissatisfaction. Greater body image dissatisfaction was also associated with poorer quality of life. However, the methodological and reporting quality of studies was in some cases poor with considerable heterogeneity. Future IBD research should incorporate measurement of body image dissatisfaction using validated tools.
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