Gea A. Holtman

Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis

BACKGROUND: The clinical presentation of pediatric inflammatory bowel disease (IBD) is often nonspecific and overlaps with functional gastrointestinal disorders. OBJECTIVE: To determine the diagnostic accuracy of symptoms, signs, noninvasive tests, and test combinations that can assist the clinician with the diagnosis of IBD in symptomatic children. METHODS: A literature search was conducted of Medline and Embase. Two reviewers independently selected studies reporting on the diagnostic accuracy of tests for IBD, with confirmation by endoscopy and histopathology or clinical follow-up, in children with chronic gastrointestinal symptoms. Two reviewers independently extracted data and assessed study quality with the QUADAS-2, an evidence-based quality assessment tool for diagnostic accuracy studies. RESULTS: Nineteen studies were included (N = 2806). Symptoms (abdominal pain, diarrhea, rectal bleeding, and weight loss) had pooled sensitivities ranging from 0.48 to 0.82 and specificities ranging from 0.17 to 0.78. Of all the blood markers, C-reactive protein (CRP) (9 studies) and albumin (6 studies) had the best performance, with pooled sensitivities of 0.63 (0.51–0.73) and 0.48 (0.31–0.66), respectively, and specificities of 0.88 (0.80–0.93) and 0.94 (0.86–0.98). Assessment of fecal calprotectin (FCal) (10 studies) had a pooled sensitivity of 0.99 (0.92–1.00) and a specificity of 0.65 (0.54–0.74). One limitation was that none of the studies was conducted in nonreferred children. CONCLUSIONS: In children whose pediatrician is considering an endoscopy, symptoms are not accurate enough to identify low-risk patients in whom an endoscopy can be avoided. FCal, CRP, and albumin findings are potentially of clinical value, given their ability to select children at low risk (negative FCal test result) or high risk (positive CRP or albumin test result) for IBD.

Avoid Endoscopy in Children With Suspected Inflammatory Bowel Disease Who Have Normal Calprotectin Levels

ABSTRACT In children with suspected inflammatory bowel disease, adding calprotectin stool testing to the screening strategy has been recommended to distinguish organic from nonorganic disease. In this cohort study with historical controls, we could not confirm that screening with stool calprotectin improves the diagnostic yield (ratio inflammatory bowel disease–positive endoscopies and total number of endoscopies); however, in patients with normal fecal calprotectin levels (<50 &mgr;g/g) endoscopic and histological abnormalities were not seen. We propose to refrain from endoscopy when stool calprotectin levels are normal.

Diagnostic Accuracy of Fecal Calprotectin for Pediatric Inflammatory Bowel Disease in Primary Care: A Prospective Cohort Study

PURPOSE In specialist care, fecal calprotectin (FCal) is a commonly used noninvasive diagnostic test for ruling out inflammatory bowel disease (IBD) in children with chronic gastrointestinal symptoms. The aim of this study was to evaluate the diagnostic accuracy of FCal for IBD in symptomatic children in primary care. METHODS We studied 2 prospective cohorts of children with chronic diarrhea, recurrent abdominal pain, or both: children initially seen in primary care (primary care cohort) and children referred to specialist care (referred cohort). FCal (index test) was measured at baseline and compared with 1 of the 2 reference standards for IBD: endoscopic assessment or 1-year follow-up. Physicians were blinded to FCal results, and values greater than 50 μg/g feces were considered positive. We determined specificity in the primary care cohort and sensitivity in the referred cohort. RESULTS None of the 114 children in the primary care cohort ultimately received a diagnosis of IBD. The specificity of FCal in the primary care cohort was 0.87 (95% CI, 0.80–0.92). Among the 90 children in the referred cohort, 17 (19%) ultimately received a diagnosis of IBD. The sensitivity of FCal in the referred cohort was 0.99 (95% CI, 0.81–1.00). CONCLUSIONS The findings of this study suggest that a positive FCal result in children with chronic gastrointestinal symptoms seen in primary care is not likely to be indicative of IBD. A negative FCal result is likely to be a true negative, which safely rules out IBD in children in whom a primary care physician considers referral to specialist care.

Challenges in diagnostic accuracy studies in primary care: The fecal calprotectin example

BackgroundLow disease prevalence and lack of uniform reference standards in primary care induce methodological challenges for investigating the diagnostic accuracy of a test. We present a study design that copes with these methodological challenges and discuss the methodological implications of our choices, using a quality assessment tool for diagnostic accuracy studies (QUADAS-2).DesignThe study investigates the diagnostic value of fecal calprotectin for detecting inflammatory bowel disease in children presenting with chronic gastrointestinal symptoms in primary care. It is a prospective cohort study including two cohorts of children: one cohort will be recruited in primary care and the other in secondary/tertiary care. Test results of fecal calprotectin will be compared to one of the two reference standards for inflammatory bowel disease: endoscopy with histopathological examination of mucosal biopsies or assessment of clinical symptoms at 1-year follow-up.DiscussionAccording to QUADAS-2 the use of two reference standards and the recruitment of patients in two populations may cause differential verification bias and spectrum bias, respectively. The clinical relevance of this potential bias and methods to adjust for this are presented. This study illustrates the importance of awareness of the different kinds of bias that result from choices in the design phase of a diagnostic study in a low prevalence setting. This approach is exemplary for other diagnostic research in primary care.

Dientamoeba fragilis colonization is not associated with gastrointestinal symptoms in children at primary care level

Background. Dientamoeba fragilis is commonly identified in children in primary care and is suspected to cause gastrointestinal disease. Objective. To determine the association between D. fragilis colonization and gastrointestinal symptoms in children. Methods. We performed a cross-sectional study with children who presented in primary care with gastrointestinal symptoms. The associations between D. fragilis colonization and specific symptoms were explored by means of logistic regression analyses. Asymptomatic siblings of these cases were invited as control subjects for a case–control analysis, where we explored the association between D. fragilis and gastrointestinal symptoms with conditional logistic regression analysis. Results. In the cross-sectional study, 107 children were included. Their median age was 9 years (interquartile range = 6–12) and 38 (35.5%) were boys. Colonization of D. fragilis was present in 59 children (55.1%). The absence of D. fragilis was associated with soft to watery stool [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.10–0.85], chronic diarrhoea (OR = 0.42; 95% CI = 0.18–0.97) and fatigue (OR = 0.45; 95% CI = 0.20–0.99). The case–control analyses included 44 children in each group. Dientamoeba fragilis colonization was not observed more often in cases than in controls after adjustment for age and sex (OR = 1.02; 95% CI = 0.28–3.65). Conclusion. Dientamoeba fragilis is a common parasite in children with and without gastrointestinal symptoms. The anomalous finding of the association between the absence of D. fragilis with soft to watery stools, chronic diarrhoea and fatigue are inexplicable. Our study suggests that D. fragilis colonization does not increase the risk for gastrointestinal symptoms.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with head and neck tumors, a systematic review and meta-analysis

Background Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic meta-analysis. Data sources Pubmed, EMBASE and Web of Science were searched from their first record to September 23th 2014. Study selection Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when ≥5 studies per test were included. Data synthesis We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95%CI 72–92) and specificity of 82% (71–89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74–96) and specificity of 86% (69–94). Limitations Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis

ObjectiveTreatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas.MethodsDatabases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included.ResultsAnatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51–81) and 77% (45–93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60–80) and specificity of 87% (77–93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82–91) with a specificity of 86% (77–91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73–98) and specificity was 85% (76–92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79–97) and specificity was 95% (65–99).ConclusionAdvanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas.Key points• Treatment response assessment in high-grade gliomas with anatomical MRI is unreliable• Novel advanced MRI techniques have been studied, but diagnostic accuracy is unknown• Meta-analysis demonstrates that advanced MRI showed higher diagnostic accuracy than anatomical MRI• Highest diagnostic accuracy for spectroscopy and perfusion MRI• Supports the incorporation of advanced MRI in high-grade glioma treatment response assessment

Attention, arousal and other rapid bedside screening instruments for delirium in older patients: a systematic review of test accuracy studies

Objective delirium occurs frequently in frail patients but is easily missed. Screening with a rapid, easy-to-use and highly sensitive instrument might help improve recognition. The aim of this study was to review attention, arousal and other rapid bedside screening instruments for delirium in older patients. Methods a literature search was performed in PubMed, PsycINFO and Embase. We scrutinized forward citations in Google Scholar, and references of included articles and prior reviews. We included studies among older patients that investigated the sensitivity and specificity of delirium screening instruments that could be administered in 3 min or less, and did not require surrogate information. We extracted study characteristics, risk of bias, sensitivity and specificity. Results we identified 27 studies among 4,766 patients in hospitals and nursing homes. They tested many different single and several combined screening instruments. Prevalence of delirium varied between 4% and 57%. Only one study scored a low risk of bias on all domains. Sensitivity varied between 17% and 100%, and specificity between 38% and 99%. Of the 22 tests with sensitivity ≥90%, seven also had specificity ≥80% in older patients in general. These results were approximately reproduced for the Observational Scale of Level of Arousal (OSLA) and Richmond Agitation and Sedation Scale (RASS): sensitivity and specificity were >80%. Conclusion two arousal tests-OSLA and RASS-had reproduced high sensitivity and specificity in older patients. Nurses can administer these tests during daily interaction with patients. Test accuracy studies about rapid screening tools for delirium superimposed on dementia were scarce.

Diagnostic test strategies in children at increased risk of inflammatory bowel disease in primary care

Background In children with symptoms suggestive of inflammatory bowel disease (IBD) who present in primary care, the optimal test strategy for identifying those who require specialist care is unclear. We evaluated the following three test strategies to determine which was optimal for referring children with suspected IBD to specialist care: 1) alarm symptoms alone, 2) alarm symptoms plus c-reactive protein, and 3) alarm symptoms plus fecal calprotectin. Methods A prospective cohort study was conducted, including children with chronic gastrointestinal symptoms referred to pediatric gastroenterology. Outcome was defined as IBD confirmed by endoscopy, or IBD ruled out by either endoscopy or unremarkable clinical 12 month follow-up with no indication for endoscopy. Test strategy probabilities were generated by logistic regression analyses and compared by area under the receiver operating characteristic curves (AUC) and decision curves. Results We included 90 children, of whom 17 (19%) had IBD (n = 65 from primary care physicians, n = 25 from general pediatricians). Adding fecal calprotectin to alarm symptoms increased the AUC significantly from 0.80 (0.67–0.92) to 0.97 (0.93–1.00), but adding c-reactive protein to alarm symptoms did not increase the AUC significantly (p > 0.05). Decision curves confirmed these patterns, showing that alarm symptoms combined with fecal calprotectin produced the diagnostic test strategy with the highest net benefit at reasonable threshold probabilities. Conclusion In primary care, when children are identified as being at high risk for IBD, adding fecal calprotectin testing to alarm symptoms was the optimal strategy for improving risk stratification.

Development and validation of a clinical prediction tool to estimate the individual risk of depressive relapse or recurrence in individuals with recurrent depression

OBJECTIVES Many studies examined predictors of depressive relapse/recurrence but no simple tool based on well-established risk factors is available that estimates the risk within an individual. We developed and validated such a prediction tool in remitted recurrently depressed individuals. METHODS The tool was developed using data (n = 235) from a pragmatic randomised controlled trial in remitted recurrently depressed participants and externally validated using data (n = 209) from a similar randomised controlled trial of remitted recurrently depressed participants using maintenance antidepressants. Cox regression was used with time to relapse/recurrence within 2 years as outcome and well-established risk factors as predictors. Performance measures and absolute risk scores were calculated, a practically applicable risk score was created, and the tool was externally validated. RESULTS The 2-year cumulative proportion relapse/recurrence was 46.2% in the validation dataset. The tool included number of previous depressive episodes, residual depressive symptoms, severity of the last depressive episode, and treatment. The C-statistic and calibration slope were 0.56 and 0.81 respectively. The tool stratified participants into relapse/recurrence risk classes of 37%, 55%, and 72%. The C-statistic and calibration slope in the external validation were 0.59 and 0.56 respectively, and Kaplan Meier curves showed that the tool could differentiate between risk classes. CONCLUSIONS This is the first study that developed a simple prediction tool based on well-established risk factors of depressive relapse/recurrence, estimating the individual risk. Since the overall performance of the model was poor, more studies are needed to enhance the performance before recommending implementation into clinical practice.