Eosinophilic airway inflammation is associated with increased corticosteroid responsiveness in asthma, but direct airway sampling methods are invasive or laborious. Minimally invasive markers for ...airway eosinophilia could present an alternative method, but estimates of their accuracy vary.
We did a systematic review and searched Medline, Embase, and PubMed for studies assessing the diagnostic accuracy of markers against a reference standard of induced sputum, bronchoalveolar lavage, or endobronchial biopsy in patients with asthma or suspected asthma (for inception to Aug 1, 2014). Unpublished results were obtained by contacting authors of studies that did not report on diagnostic accuracy, but had data from which estimates could be calculated. We assessed risk of bias with QUADAS-2. We used meta-analysis to produce summary estimates of accuracy.
We included 32 studies: 24 in adults and eight in children. Of these, 26 (81%) showed risk of bias in at least one domain. In adults, three markers had extensively been investigated: fraction of exhaled nitric oxide (FeNO) (17 studies; 3216 patients; summary area under the receiver operator curve AUC 0·75 95% CI 0·72-0·78); blood eosinophils (14 studies; 2405 patients; 0·78 0·74-0·82); total IgE (seven studies; 942 patients; 0·65 0·61-0·69). In children, only FeNO (six studies; 349 patients; summary AUC 0·81 0·72-0·89) and blood eosinophils (three studies; 192 patients; 0·78 0·71-0·85) had been investigated in more than one study. Induced sputum was most frequently used as the reference standard. Summary estimates of sensitivity and specificity in detecting sputum eosinophils of 3% or more in adults were: 0·66 (0·57-0·75) and 0·76 (0·65-0·85) for FeNO; 0·71 (0·65-0·76) and 0·77 (0·70-0·83) for blood eosinophils; and 0·64 (0·42-0·81) and 0·71 (0·42-0·89) for IgE.
FeNO, blood eosinophils, and IgE have moderate diagnostic accuracy. Their use as a single surrogate marker for airway eosinophilia in patients with asthma will lead to a substantial number of false positives or false negatives.
None.
Lipoprotein(a) Lp(a) is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density ...lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a).
We conducted a systematic review and meta-analysis of randomized trials with a statin and placebo arm. Medline and EMBASE were searched until August 2019. Quality assessment of studies was done using Cochrane risk-of-bias tool (RoB 2). Mean difference of absolute and percentage changes of Lp(a) in the statin vs. the placebo arms were pooled using a random-effects meta-analysis. We compared effects of different types and intensities of statin therapy using subgroup- and network meta-analyses. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Overall, 39 studies (24 448 participants) were included. Mean differences (95% confidence interval) of absolute and percentage changes in the statin vs. the placebo arms were 1.1 mg/dL (0.5-1.6, P < 0.0001) and 0.1% (-3.6% to 4.0%, P = 0.95), respectively (moderate-certainty evidence). None of the types of statins changed Lp(a) significantly compared to placebo (very low- to high-certainty evidence), as well as intensities of statin therapy (low- to moderate-certainty evidence).
Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk.
Guidelines recommend endosonography with fine-needle aspiration for mediastinal nodal staging in non-small-cell lung cancer, but most do not specify whether this should be through endobronchial ...endoscopy (EBUS), oesophageal endoscopy (EUS), or both. We assessed the added value and diagnostic accuracy of the combined use of EBUS and EUS.
For this systematic review and random effects meta-analysis, we searched MEDLINE, Embase, BIOSIS Previews, and Web of Science, without language restrictions, for studies published between Jan 1, 2000, and Feb 25, 2016. We included studies that assessed the accuracy of the combined use of EBUS and EUS in detecting mediastinal nodal metastases (N2/N3 disease) in patients with lung cancer. For each included study, we extracted data on the age and sex of participants, inclusion criteria regarding tumour stage on imaging, details of the endoscopic testing protocol, duration of each endoscopic procedure, number of lymph nodes sampled, serious adverse events occurring during the endoscopic procedures, the reference standard, and 2 × 2 tables for EBUS, EUS, and the combined approach. We evaluated the added value (absolute increase in sensitivity and in detection rate) of the combined use of EBUS and EUS in detecting mediastinal nodal metastases over either test alone, and the diagnostic accuracy (sensitivity and negative predictive value) of the combined approach. This study is registered with PROSPERO, number CRD42015019249.
We identified 2567 unique manuscripts by database search, of which 13 studies (including 2395 patients) were included in the analysis. Median prevalence of N2/N3 disease was 34% (range 23-71). On average, addition of EUS to EBUS increased sensitivity by 0·12 (95% CI 0·08-0·18) and addition of EBUS to EUS increased sensitivity by 0·22 (0·16-0·29). Mean sensitivity of the combined approach was 0·86 (0·81-0·90), and the mean negative predictive value was 0·92 (0·89-0·93). The mean negative predictive value was significantly higher in studies with a prevalence of 34% or less (0·93 95% CI 0·91-0·95) compared with studies with a prevalence of more than 34% (0·89 0·85-0·91; p=0·013). We found no significant differences in mean sensitivity and negative predictive value between studies that did EBUS first or EUS first, or between studies that used an EBUS-scope or a regular echoendoscope to do EUS.
The combined use of EBUS and EUS significantly improves sensitivity in detecting mediastinal nodal metastases, reducing the need for surgical staging procedures.
No external funding.
Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing ...quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Decision aids have been overall successful in improving the quality of health decision making. However, it is unclear whether the impact of the results of using decision aids also apply to older ...people (aged 65+). We sought to systematically review randomized controlled trials (RCTs) and clinical controlled trials (CCTs) evaluating the efficacy of decision aids as compared to usual care or alternative intervention(s) for older adults facing treatment, screening or care decisions.
A systematic search of (1) a Cochrane review of decision aids and (2) MEDLINE, Embase, PsycINFO, Cochrane library central registry of studies and Cinahl. We included published RCTs/CCTs of interventions designed to improve shared decision making (SDM) by older adults (aged 65+) and RCTs/CCTs that analysed the effect of the intervention in a subgroup with a mean age of 65+. Based on the International Patient Decision aid Standards (IPDAS), the primary outcomes were attributes of the decision and the decision process. Other behavioral, health, and health system effects were considered as secondary outcomes. If data could be pooled, a meta-analysis was conducted. Data for which meta-analysis was not possible were synthesized qualitatively.
The search strategy yielded 11,034 references. After abstract and full text screening, 22 papers were included. Decision aids performed better than control resp. usual care interventions by increasing knowledge and accurate risk perception in older people (decision attributes). With regard to decision process attributes, decision aids resulted in lower decisional conflict and more patient participation.
This review shows promising results on the effectiveness of decision aids for older adults. Decision aids improve older adults' knowledge, increase their risk perception, decrease decisional conflict and seem to enhance participation in SDM. It must however be noted that the body of literature on the effectiveness of decision aids for older adults is still in its infancy. Only one decision aid was specifically developed for older adults, and the mean age in most studies was between 65 and 70, indicating that the oldest-old were not included. Future research should expand on the design, application and evaluation of decision aids for older, more vulnerable adults.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
A large proportion of proton pump inhibitor (PPI) prescriptions, including those for stress ulcer prophylaxis (SUP), are inappropriate. Our study purpose was to systematically review the ...effectiveness of de-implementation strategies aimed at reducing inappropriate PPI use for SUP in hospitalized, non-intensive care unit (non-ICU) patients.
Methods
We searched MEDLINE and Embase databases (from inception to January 2020). Two authors independently screened references, performed data extraction, and critical appraisal. Randomized trials and comparative observational studies were eligible for inclusion. Criteria developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group were used for critical appraisal. Besides the primary outcome (inappropriate PPI prescription or use), secondary outcomes included (adverse) pharmaceutical effects and healthcare use.
Results
We included ten studies in this review. Most de-implementation strategies contained an educational component (meetings and/or materials), combined with either clinical guideline implementation (
n
= 5), audit feedback (
n
= 3), organizational culture (
n
= 4), or reminders (
n
= 1). One study evaluating the de-implementation strategy effectiveness showed a significant reduction (RR 0.14; 95% CI 0.03–0.55) of new inappropriate PPI prescriptions. Out of five studies evaluating the effectiveness of de-implementing inappropriate PPI use, four found a significant reduction (RR 0.21; 95% CI 0.18–0.26 to RR 0.76; 95% CI 0.68–0.86). No significant differences in the occurrence of pharmaceutical effects (
n
= 1) and in length of stay (
n
= 3) were observed. Adverse pharmaceutical effects were reported in two studies and five studies reported on PPI or total drug costs. No pooled effect estimates were calculated because of large statistical heterogeneity between studies.
Discussion
All identified studies reported mainly educational interventions in combination with one or multiple other intervention strategies and all interventions were targeted at providers. Most studies found a small to moderate reduction of (inappropriate) PPI prescriptions or use.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of ...active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
ObjectiveKnowledge gaps regarding hyperemesis gravidarum (HG) are substantial. We aimed to systematically identify and map recent evidence addressing the top 10 priority questions for HG, as ...published in 2021 in a James Lind Alliance Priority Setting Partnership.DesignSystematic evidence map.MethodsWe searched MEDLINE and EMBASE on 12 January 2021 and CINAHL on 22 February 2021 with search terms hyperemesis gravidarum, pernicious vomiting in pregnancy and their synonyms. Results were limited to 2009 onwards. Two reviewers independently screened titles and abstracts to assess whether the studies addressed a top 10 priority questions for HG. Differences were discussed until consensus was reached. Publications were allocated to one or more top 10 research questions. Study design was noted, as was patient or public involvement. Two reviewers extracted data synchronously and both cross-checked 10%. Extracted data were imported into EPPI-Reviewer software to create an evidence map.Outcome measuresThe number and design of studies in the search yield, displayed per the published 10 priority questions.ResultsSearches returned 4338 results for screening; 406 publications were included in the evidence map. 136 publications addressed multiple questions. Numerous studies address the immediate and long-term outcomes or possible markers for HG (question 8 and 9, respectively 164 and 82 studies). Very few studies seek a possible cure for HG (question 1, 8 studies), preventative treatment (question 4, 2 studies) or how to achieve nutritional requirements of pregnancy (question 10, 17 studies). Case reports/series were most numerous with 125 (30.7%) included. Few qualitative studies (9, 2.2%) were identified. 25 (6.1%) systematic reviews addressed eight questions, or aspects of them. 31 (7.6%) studies included patient involvement.ConclusionsThere are significant gaps and overlap in the current HG literature addressing priority questions. Researchers and funders should direct their efforts at addressing the gaps in the top 10 questions.
With the exponential growth of published systematic reviews (SR), there is a high potential for overlapping and redundant duplication of work. Prospective protocol registration gives the opportunity ...to assess the added value of a new study or review, thereby potentially reducing research waste and simultaneously increasing transparency and research quality. The PROSPERO database for SR protocol registration was launched 10 years ago. This study aims to assess the proportion SRs of intervention studies with a protocol registration (or publication) and explore associations of SR characteristics with protocol registration status.
PubMed was searched for SRs of human intervention studies published in January 2020 and January 2021. After random-stratified sampling and eligibility screening, data extraction on publication and journal characteristics, and protocol registration status, was performed. Both descriptive and multivariable comparative statistical analyses were performed.
A total of 357 SRs (2020: n = 163; 2021: n = 194) were included from a random sample of 1267 publications. Of the published SRs, 38% had a protocol. SRs that reported using PRISMA as a reporting guideline had higher odds of having a protocol than publications that did not report PRISMA (OR 2.71; 95% CI: 1.21 to 6.09). SRs with a higher journal impact factor had higher odds of having a protocol (OR 1.12; 95% CI 1.04 to 1.25). Publications from Asia had a lower odds of having a protocol (OR 0.43; 95% CI 0.23 to 0.80, reference category = Europe). Of the 33 SRs published in journals that endorse PROSPERO, 45% did not have a protocol. Most SR protocols were registered in PROSPERO (n = 129; 96%).
We found that 38% of recently published SRs of interventions reported a registered or published protocol. Protocol registration was significantly associated with a higher impact factor of the journal publishing the SR and a more frequent self-reported use of the PRISMA guidelines. In some parts of the world, SR protocols are more often registered or published than others. To guide strategies to increase the uptake of SR protocol registration, further research is needed to gain understanding of the benefits and informativeness of SRs protocols among different stakeholders.
osf.io/9kj7r/.
Background
The clinical implications of SARS‐CoV‐2 infection are highly variable. Some people with SARS‐CoV‐2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID‐19 ...and COVID‐19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID‐19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020.
Objectives
To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID‐19 clinics, has COVID‐19.
Search methods
For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID‐19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions.
Selection criteria
Studies were eligible if they included patients with clinically suspected COVID‐19, or if they recruited known cases with COVID‐19 and controls without COVID‐19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS‐CoV‐2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards.
Data collection and analysis
Pairs of review authors independently selected all studies, at both title and stage and full‐text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS‐2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random‐effects meta‐analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable.
Main results
We identified 44 studies including 26,884 participants in total. Prevalence of COVID‐19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID‐19, so we present the results for all disease severities together.
Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies.
The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID‐19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults.
We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93).
Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09).
Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%).
Authors' conclusions
The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID‐19. The presence of anosmia or ageusia may be useful as a red flag for COVID‐19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing.
Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID‐19, are still urgently needed. Results from such studies could inform subsequent management decisions.
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