Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis.

BACKGROUND: Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE: This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS: Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 µg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS: ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

Right Ventricular Assist Device With an Oxygenator for the Management of Combined Right Ventricular and Respiratory Failure: A Systematic Review.

BACKGROUND: Severe lung disease frequently presents with both refractory hypoxemia and right ventricular (RV) failure. Right ventricular assist device with an oxygenator (OxyRVAD) is an extracorporeal membrane oxygenation (ECMO) configuration of RV bypass that also supplements gas exchange. This systematic review summarises the available literature regarding the use of OxyRVAD in the setting of severe lung disease with associated RV failure. METHODS: PubMed, Embase, and Google Scholar were queried on September 27, 2023, for articles describing the use of an OxyRVAD configuration. The main outcome of interest was survival to intensive care unit (ICU) discharge. Data on the duration of OxyRVAD support and device-related complications were also recorded. RESULTS: Out of 475 identified articles, 33 were retained for analysis. Twenty-one articles were case reports, and 12 were case series, representing a total of 103 patients. No article provided a comparison group. Most patients (76.4%) were moved to OxyRVAD from another type of mechanical support. OxyRVAD was used as a bridge to transplant or curative surgery in 37.4% and as a bridge to recovery or decision in 62.6%. Thirty-one patients (30.1%) were managed with the dedicated single-access dual-lumen ProtekDuo cannula. Median time on OxyRVAD was 12 days (interquartile range 8-23 days), and survival to ICU discharge was 63.9%. Device-related complications were infrequently reported. CONCLUSION: OxyRVAD support is a promising alternative for RV support when gas exchange is compromised, with good ICU survival in selected cases. Comparative analyses in patients with RV failure with and without severe lung disease are needed.

Investigating the Impact of Stress on Pain: A Scoping Review on Sense of Control, Social-Evaluative Threat, Unpredictability, and Novelty (STUN Model).

Background: Stress can have paradoxical effects on pain, namely hyperalgesia and hypoalgesia. Four situational characteristics activate the hypothalamic-pituitary-adrenal axis, leading to a physiological stress response: lacking Sense of control, social-evaluative Threat, Unpredictability and Novelty (STUN). This scoping review reports on the types of evidence published on the effects of STUN characteristics on pain outcomes. Databases/Data Treatment: Searches of primary electronic databases were performed to identify articles published on adults between 1990 and 2021 that contained search terms on pain and stress/STUN characteristics. A total of 329 articles were included in the analysis. Results: Only 3.3% of studies examined simultaneously >1 STUN component. Almost all observational studies (177/180) examined the association between perceived stress and pain without measuring physiological stress responses. Of the 130 experimental studies, 78 (60.0%) manipulated stressful characteristics through nociception, and only 38.5% assessed if/how stress manipulation impacted perceived stress. Conclusion: There is a clear lack of integration of the characteristics that trigger a physiological stress response in the pain field. Only 3.3% of studies examined simultaneously more than one STUN component and there is an unequal attention given to individual components of the STUN framework. Recommendations for future research include selection of stress manipulations/measurements that are more precisely inducing/reflecting neurobiological mechanisms of stress responses to insure valid integration of scientific knowledge.

Computer-assisted analysis of routine EEG to identify hidden biomarkers of epilepsy: A systematic review.

Background: Computational analysis of routine electroencephalogram (rEEG) could improve the accuracy of epilepsy diagnosis. We aim to systematically assess the diagnostic performances of computed biomarkers for epilepsy in individuals undergoing rEEG. Methods: We searched MEDLINE, EMBASE, EBM reviews, IEEE Explore and the grey literature for studies published between January 1961 and December 2022. We included studies reporting a computational method to diagnose epilepsy based on rEEG without relying on the identification of interictal epileptiform discharges or seizures. Diagnosis of epilepsy as per a treating physician was the reference standard. We assessed the risk of bias using an adapted QUADAS-2 tool. Results: We screened 10 166 studies, and 37 were included. The sample size ranged from 8 to 192 (mean=54). The computed biomarkers were based on linear (43%), non-linear (27%), connectivity (38%), and convolutional neural networks (10%) models. The risk of bias was high or unclear in all studies, more commonly from spectrum effect and data leakage. Diagnostic accuracy ranged between 64% and 100%. We observed high methodological heterogeneity, preventing pooling of accuracy measures. Conclusion: The current literature provides insufficient evidence to reliably assess the diagnostic yield of computational analysis of rEEG. Significance: We provide guidelines regarding patient selection, reference standard, algorithms, and performance validation.

Screening for cognitive impairment in adults with sickle cell disease: A systematic review and meta-analysis.

Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning.  Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.

A Systematic Review and Meta-Analysis on Sex-Based Disparities in Patients with Chronic Limb Threatening Ischemia Undergoing Revascularization.

BACKGROUND: This systematic review and meta-analysis sought to describe the prognostic implications of sex on the clinical outcomes of patients undergoing interventions for chronic limb threatening ischemia (CLTI). METHODS: Studies were systematically searched across 7 databases from inception to August 25, 2021 and rerun on October 11, 2022. Studies focusing on patients with CLTI undergoing open surgery, endovascular treatment (EVT), or hybrid procedures were included if sex-based differences were associated with a clinical outcome. Two independent reviewers screened studies for inclusion, extracted data, and assessed risk of bias using the Newcastle-Ottawa scale. Primary outcomes included inpatient mortality, major adverse limb events (MALE), and amputation-free survival (AFS). Meta-analyses were performed using random effects models and reported pooled odds ratio (pOR) and 95% confidence interval (CI). RESULTS: A total of 57 studies were included in the analysis. A meta-analysis of 6 studies demonstrated that female sex was associated with statistically higher inpatient mortality compared to male sex undergoing open surgery or EVT (pOR, 1.17; 95% CI: 1.11-1.23). Female sex also demonstrated a trend toward increased limb loss in those undergoing EVT (pOR, 1.15; 95% CI: 0.91-1.45) and open surgery (pOR 1.46; 95% CI: 0.84-2.55). Female sex also had a trend toward higher MALE (pOR, 1.06; 95% CI, 0.92-1.21) in 6 studies. Finally, female sex had a trend toward worse AFS (pOR, 0.85; 95% CI, 0.70-1.03) in 8 studies. CONCLUSIONS: Female sex was significantly associated with higher inpatient mortality and a trend toward higher MALE following revascularization. Female sex trended toward worse AFS. The reasons for these disparities are likely multifaceted on patient, provider, and systemic levels and should be explored to identify solutions for decreasing these health inequities across this vulnerable patient population.

Computer-assisted analysis of routine electroencephalogram to identify hidden biomarkers of epilepsy: protocol for a systematic review.

INTRODUCTION: The diagnosis of epilepsy frequently relies on the visual interpretation of the electroencephalogram (EEG) by a neurologist. The hallmark of epilepsy on EEG is the interictal epileptiform discharge (IED). This marker lacks sensitivity: it is only captured in a small percentage of 30 min routine EEGs in patients with epilepsy. In the past three decades, there has been growing interest in the use of computational methods to analyse the EEG without relying on the detection of IEDs, but none have made it to the clinical practice. We aim to review the diagnostic accuracy of quantitative methods applied to ambulatory EEG analysis to guide the diagnosis and management of epilepsy. METHODS AND ANALYSIS: The protocol complies with the recommendations for systematic reviews of diagnostic test accuracy by Cochrane. We will search MEDLINE, EMBASE, EBM reviews, IEEE Explore along with grey literature for articles, conference papers and conference abstracts published after 1961. We will include observational studies that present a computational method to analyse the EEG for the diagnosis of epilepsy in adults or children without relying on the identification of IEDs or seizures. The reference standard is the diagnosis of epilepsy by a physician. We will report the estimated pooled sensitivity and specificity, and receiver operating characteristic area under the curve (ROC AUC) for each marker. If possible, we will perform a meta-analysis of the sensitivity and specificity and ROC AUC for each individual marker. We will assess the risk of bias using an adapted QUADAS-2 tool. We will also describe the algorithms used for signal processing, feature extraction and predictive modelling, and comment on the reproducibility of the different studies. ETHICS AND DISSEMINATION: Ethical approval was not required. Findings will be disseminated through peer-reviewed publication and presented at conferences related to this field. PROSPERO REGISTRATION NUMBER: CRD42022292261.

Diagnostic yield of CT head in delirium and altered mental status-A systematic review and meta-analysis.

BACKGROUND: CT head is commonly performed in the setting of delirium and altered mental status (AMS), with variable yield. We aimed to evaluate the yield of CT head in hospitalized patients with delirium and/or AMS across a variety of clinical settings and identify factors associated with abnormal imaging. METHODS: We included studies in adult hospitalized patients, admitted to the emergency department (ED) and inpatient medical unit (grouped together) or the intensive care unit (ICU). Patients had a diagnosis of delirium/AMS and underwent a CT head that was classified as abnormal or not. We searched Medline, Embase and other databases (informed by PRISMA guidelines) from inception until November 11, 2021. Studies that were exclusively performed in patients with trauma or a fall were excluded. A meta-analysis of proportions was performed; the pooled proportion of abnormal CTs was estimated using a random effects model. Heterogeneity was determined via the I2 statistic. Factors associated with an abnormal CT head were summarized qualitatively. RESULTS: Forty-six studies were included for analysis. The overall yield of CT head in the inpatient/ED was 13% (95% CI: 10.2%-15.9%) and in ICU was 17.4% (95% CI: 10%-26.3%), with considerable heterogeneity (I2 96% and 98% respectively). Heterogeneity was partly explained after accounting for study region, publication year, and representativeness of the target population. Yield of CT head diminished after year 2000 (19.8% vs. 11.1%) and varied widely depending on geographical region (8.4%-25.9%). The presence of focal neurological deficits was a consistent factor that increased yield. CONCLUSION: Use of CT head to diagnose the etiology of delirium and AMS varied widely and yield has declined. Guidelines and clinical decision support tools could increase the appropriate use of CT head in the diagnostic etiology of delirium/AMS.

Percutaneous Mechanical Circulatory Support in Post-Myocardial Infarction Cardiogenic Shock: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiogenic shock (CS) complicates 5%-10% of acute myocardial infarction (AMI) and is the leading cause of early mortality. It remains unclear whether percutaneous mechanical support (pMCS) devices improve post-AMI CS outcome. METHODS: A systematic review of original studies comparing the effect of pMCS on AMI-CS mortality was conducted with the use of Medline, Embase, Google Scholar, and the Cochrane Library databases. RESULTS: Of 8672 records, 50 were retained for quantitative analysis. Four additional references were added from other sources. Four references reported a significant mortality reduction with intra-aortic balloon pump (IABP) in patients with failed primary percutaneous coronary intervention (pPCI) or managed with thrombolysis. Meta-analyses showed no advantage of Impella over conventional therapy (pooled OR 0.55, 95% CI 0.20-1.46; I2 = 0.85) and increased mortality compared with IABP (pooled OR 1.32; 95% CI 1.08-1.62; I2 = 0.85). No study reported a mortality advantage for extracorporeal membrane oxygenation (ECMO) over conventional therapy, IABP, or Impella support. Early mortality might be improved with the addition of IABP or Impella to ECMO. Bleeding Academic Research Consortium ≥ 3 bleeding was increased with every pMCS strategy. CONCLUSIONS: The current evidence is of poor to moderate quality, with only 1 in 5 included articles reporting randomised data and several reporting unadjusted outcomes. Yet, there is some evidence to favour IABP use in the setting of thrombolysis or with failed pPCI, and adding IABP or Impella should be considered for patients requiring ECMO.

Development of a patient-reported outcome measure of recovery after abdominal surgery: a hypothesized conceptual framework.

BACKGROUND: We initiated a research program to develop a novel patient-reported outcome measure (PROM) to assess postoperative recovery from the perspective of abdominal surgery patients. In light of FDA recommendations, the first stage of our program aimed to, based on previous literature and expert input, develop a hypothesized conceptual framework portraying the health domains that are potentially relevant to the process of recovery after abdominal surgery. METHODS: This study was conducted in three phases: (1) systematic review to identify PROMs with measurement properties appraised in the context of recovery after abdominal surgery, (2) content analysis to categorize the health domains covered by the PROMs according to the ICF, and (3) two-round Delphi study to gain expert input regarding which of these health domains are relevant to the process of recovery. Participants were experts in perioperative care identified through two major surgical societies (35 invited). RESULTS: The systematic review identified 19 PROMs covering 66 ICF domains. 23 experts (66%) participated in the Delphi process. After Round 2, experts agreed that 22 health domains (8 body functions, 14 activities and participation) are potentially relevant to the process of recovery after abdominal surgery. These domains were organized into a diagram, representing our hypothesized conceptual framework. CONCLUSIONS: This hypothesized conceptual framework is an important first step in our research program and will be further refined based on in-depth qualitative interviews with patients. The sound methodological approach used to derive this framework may be valuable for studies aimed to develop PROMs according to FDA standards.

Acute lamotrigine overdose: a systematic review of published adult and pediatric cases.

CONTEXT: Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate that lamotrigine overdose is usually benign. However, there are reported cases of cardiac arrest and mortality following lamotrigine overdose. We undertook a systematic review of the literature on lamotrigine overdoses to better understand the clinical severity, the relevance of serum concentrations, and therapeutic interventions for overdose. OBJECTIVES: To characterize manifestations of acute lamotrigine overdose, determine if serum concentrations predict poisoning severity, and evaluate the effectiveness of overdose management interventions. METHODS: We performed a literature search across eight databases, including Medline, EMBASE, and the Cochrane Library, from database inception to April 2014. Major bibliographic databases were updated on 31 May 2017. Articles were eligible if they described acute or acute on chronic lamotrigine overdose. At least one serum lamotrigine concentration had to be reported for inclusion. Reports on chronic poisoning, studies describing adverse effects of therapeutic use, and animal studies were excluded. RESULTS: We retrieved 6238 records; 48 (51 cases) met the inclusion criteria. Cases primarily involved adults (70.6%). Potentially life-threatening symptoms of overdose included seizures (55%), Glasgow Coma Scale ≤8 (20%), hypotension (12%), and wide complex tachycardia (WCT) and cardiac arrest (6%). Among the 25 cases exposed to lamotrigine alone (13 adult; 12 pediatric), 2 adult fatalities occurred (4 g and 7.5 g ingested) and 8 pediatric cases experienced seizures (all children ≤3.5-years-old, 75% without an underlying seizure disorder, ≥ 525 mg ingested). The lowest seizure-associated serum concentration was 3.8 mg/L and 25.6 mg/L for pediatric and adult patients, respectively, suggesting children may be more susceptible to CNS toxicity. Cardiovascular toxicities occurred primarily in adult patients (threshold >25 mg/L). Overdose interventions included benzodiazepines (53%), propofol or barbiturates (14%), NaHCO3 (20%), lipid therapy (12%), and extracorporeal elimination (10%). NaHCO3 yielded no response in four of nine cases with conduction delays; however, two of the four cases subsequently responded with lipid therapy. CONCLUSIONS: Most cases reporting lamotrigine exposures observed mild or no toxicity; however, large exposures were associated with severe CNS depression, seizures, cardiac conduction delays, wide complex tachycardia, and death. In adults with a serum concentration >25 mg/L, severe toxicity may occur. In patients ≤3.5 years of age, ingestions of ≥525 mg may produce severe CNS depression and seizures.

How Do We Value Postoperative Recovery?: A Systematic Review of the Measurement Properties of Patient-reported Outcomes After Abdominal Surgery.

OBJECTIVE: To appraise the level of evidence supporting the measurement properties of patient-reported outcome measures (PROMs) in the context of postoperative recovery after abdominal surgery. BACKGROUND: There is growing interest in using PROMs to support value-based care in abdominal surgery; however, to draw valid conclusions regarding patient-reported outcomes data, PROMs with robust measurement properties are required. METHODS: Eight databases (MEDLINE, EMBASE, Biosis, PsycINFO, The Cochrane Library, CINAHL, Scopus, Web of Science) were searched for studies focused on the measurement properties of PROMs in the context of recovery after abdominal surgery. The methodological quality of individual studies was evaluated using the consensus-based COSMIN checklist. Evidence supporting the measurement properties of each PROM was synthetized according to standardized criteria and compared against the International Society of Quality of Life Research minimum standards for the selection of PROMs for outcomes research. RESULTS: We identified 35 studies evaluating 22 PROMs [12 focused on nonspecific surgical populations (55%), 4 focused on abdominal surgery (18%), and 6 generic PROMs (27%)]. The great majority of the studies (74%) received only poor or fair quality ratings. Measurement properties of PROMs were predominantly supported by limited or unknown evidence. None of the PROMs fulfilled International Society of Quality of Life Research's minimum standards, hindering specific recommendations. CONCLUSIONS: There is very limited evidence supporting the measurement properties of existing PROMs used in the context of recovery after abdominal surgery. This precludes the use of these PROMs to support value-based surgical care. Further research is required to bridge this major knowledge gap. REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO): CRD42014014349.

Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses.

BACKGROUND: Low circulating levels of adiponectin, an anti-inflammatory and vasculoprotective adipokine, are associated with obesity, type 2 diabetes, and atherosclerotic disease. Presence of unstable plaques in the carotid artery is a known etiological factor causing ischemic strokes. Herein, we systematically reviewed the association between circulating adiponectin and progression of carotid atherosclerotic disease, particularly evaluating the occurrence of (1) carotid atherosclerotic plaques, (2) ischemic stroke, and (3) mortality in subjects who suffered a previous ischemic stroke. METHODS: Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The effect size and 95% confidence intervals (CIs) of the individual studies were pooled using fixed-effect or random-effect models. The quality of the eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale. Sensitivity, subgroup, and meta-regression analyses were performed to address the impact of various risk factors on the association between adiponectin and ischemic stroke risk. RESULTS: Twelve studies fulfilled the inclusion criteria for 3 independent meta-analyses. The association of increasing circulating adiponectin levels (5µg/mL-increment) with presence of carotid plaque was not conclusive (n=327; OR: 1.07; 95% CI: 0.85-1.35; 2 studies), whereas high adiponectin levels showed a significant 8% increase in risk of ischemic stroke (n=13,683; 7 studies), with a more sizable association observed among men compared to women. HDL was observed to have a marginal effect on the association between adiponectin and ischemic stroke, while other evaluated parameters were not found to be effect modifiers. A non-significant association of adiponectin with mortality was yielded (n=663; OR: 2.58; 95% CI: 0.69-9.62; 3 studies). Although no publication bias was evident, there was significant between-study heterogeneity in most analyses. CONCLUSION: It appears that the direction of the relationship between adiponectin and carotid atherosclerotic plaque presence is dependent on the duration, severity, and nature of the underlying disease, while increased adiponectin levels were associated with an increase in risk for ischemic stroke. Lastly, the results from the mortality meta-analysis remain inconclusive. Future properly designed studies are necessary to further elucidate the role of adiponectin on atherosclerotic plaque development, and its related outcomes.

Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis.

BACKGROUND: Adiponectin (APN) is an adipokine with insulin-sensitizing, anti-inflammatory, and vasculoprotective properties. Hypoadiponectinemia has been linked with disease states, such as obesity, type 2 diabetes, and cardiovascular disease. Carotid intima-media thickness (cIMT) is a strong and independent predictor of both coronary and cerebrovascular events, and has been used as a surrogate marker of subclinical atherosclerosis. The aim of this report is to systematically review the evidence on the relationship between APN and cIMT in a wide range of individuals. MATERIALS AND METHODS: Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The "sign test" and "vote count" methods were used to estimate the direction and significance of the relationship between APN and cIMT. The quality of the eligible studies was evaluated using an adapted version of the New Castle Ottawa quality assessment scale. RESULTS: Fifty-five articles fulfilled the inclusion criteria, comprised of only cross-sectional studies, including healthy subjects, general population, and individuals with metabolic, inflammatory, or other chronic diseases. Most associations between APN and cIMT followed a negative direction in the healthier and general populations, and also in cohorts with metabolic disorders and other chronic diseases, but not in those with inflammatory diseases (sign test). These associations were generally found to be weak or non-significant among all cohort groups studied (vote count). CONCLUSION: Our results are suggestive but not conclusive for an inverse association between APN levels and cIMT in diseased and non-diseased populations.

Evaluation of a Rapid Point of Care Test for Detecting Acute and Established HIV Infection, and Examining the Role of Study Quality on Diagnostic Accuracy: A Bayesian Meta-Analysis.

INTRODUCTION: Fourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta-analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy. METHODS: Two independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional). RESULTS: The overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3-99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1-93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8-100] and 99.6%, 95% CrI [99.0-99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7-99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1-44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality. CONCLUSIONS: Although the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation.

Adalimumab monotherapy versus combination therapy with immunomodulators in patients with Crohn's disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Combination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial. The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature. METHODS: We performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1 year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed. RESULTS: Eighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n=1984) showed that ADA monotherapy was inferior to combination therapy [OR=0.78 (0.64-0.96), p=0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR=1.08 (0.79-1.48), p=0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR=1.13 (0.69-1.85), p=0.62]. CONCLUSIONS: Combination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1 year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials.